Oncology Acquired Flashcards
A scientist in a clinical molecular laboratory decides to validate a qualitative assay for B-cell clonality (IGH and IGK) tests by a PCR method based on the BIOMED-2 consensus. For which one of the following malignancies is this assay NOT appropriate?
A.AML with normal karyotype and FISH
B.CLL with normal FISH
C.Follicular lymphoma with normal FISH
D.Plasma-cell myeloma with normal FISH
E.All of the above
A.AML with normal karyotype and FISH
A scientist in a clinical molecular laboratory decides to validate a qualitative assay for B-cell clonality (IGH) tests by a PCR method based on the BIOMED-2 consensus. In which one of the following situations could the results be false negative?
A.Absent or incomplete IGH rearrangements in immature B-cell neoplasms in pre-B-cell ALL
B.The presence of extensive somatic mutation in follicular lymphoma
C.Negative results caused by DNA degradation on the positive control
D.A and B
E.B and C
F.All of the above
G. None of the above
F.All of the above
A scientist in a clinical molecular laboratory decides to validate a qualitative assay for T-cell clonality (TCRG and TCRB) tests by a PCR method based on the BIOMED-2 consensus. For which one of the following malignancies is this assay NOT appropriate?
A.AML with normal karyotype and FISH
B.Follicular lymphoma with normal FISH
C.Plasma-cell myeloma with normal FISH
D.All of the above
E.None of the above
D.All of the above
The morphological and immunophenotypic findings were suspicious for extranodal marginal-zone lymphoma (such as MALT lymphoma). The MALT1 break-apart FISH was negative. Which one of the following assays would help to further establish the diagnosis if the oncologist still suspected that the patient had MALT lymphoma?
A.ALK amplification
B.BRAF V600E
C.IGH and IGK clonality tests
D.TCRG and TCRB clonality test
E.All of the above
F.None of the above
C.IGH and IGK clonality tests
A 42 yo present for nasopharyngeal mass. Histopathological examinations revealed CD3+, CD4+, CD8+, TdT+, and EBER+. The karyotype of the tumor specimen was a normal male, or 46,XY. Which one of the following assays would help to further establish the diagnosis of lymphoma?
A.ALK amplification
B.BRAF V600E
C.IGH and IGK clonality tests
D.TCRG and TCRB clonality test
E.All of the above
F.None of the above
D.TCRG and TCRB clonality test
75 yo man with neck mass. The physician ordered a test to assess clonality in the IGH gene. The result of one of the amplicons for the VH frameworks is shown for the bone marrow (A) and the mass (B) The top panel was from the bone marrow and the bottom was from the biopsy of the left neck mass. Which one of the following interpretations of the results would be the most appropriate?
A.The results of the bone-marrow biopsy indicated a clonal proliferation of B cells.
B.The results of the bone-marrow biopsy indicated a clonal proliferation of T cells.
C.The results of the biopsy from the neck mass indicated a clonal proliferation of B cells.
D.The results of the biopsy from the neck mass indicated a clonal proliferation of T cells.
E.The results of both samples indicated a clonal proliferation of B cells.
F.The results of both samples indicated a clonal proliferation of T cells.
C.The results of the biopsy from the neck mass indicated a clonal proliferation of B cells.
75 yo man with neck mass. The result of one of the amplicons for the VH frameworks are shown in Fig. 8.1. The top panel was from the bone marrow and the bottom was from the biopsy of the left neck mass. Which one of the following interpretations of the results would be the most appropriate?
A.The results indicated a clonal proliferation of B cells in the neck mass but not in the bone marrow. Therefore, the patient had B-cell lymphoma that had not metastasized into the bone marrow.
B.The results indicated a clonal proliferation of B cells in the bone marrow but not in the neck mass. Therefore, the patient had B-cell leukemia.
C.The results indicated a clonal proliferation of B cells in the neck mass but not in the bone marrow. These findings supported a diagnosis of B-cell lymphoma, but reactive lymphoproliferations cannot be completely ruled out.
D.The results indicated a clonal proliferation of B cells in the neck mass but not in the bone marrow. Therefore, the patient had B-cell lymphoma that had metastasized into the bone marrow.
E.The results indicated a clonal proliferation of B cells in bone marrow but not in the neck mass. Therefore, the patient had B-cell leukemia that had not metastasized into a remote site, such as the neck.
C.The results indicated a clonal proliferation of B cells in the neck mass but not in the bone marrow. These findings supported a diagnosis of B-cell lymphoma, but reactive lymphoproliferations cannot be completely ruled out.
7 yo with elevated WBC. A bone-marrow biopsy was obtained and revealed 30% lymphoblasts with expression of CD3, CD4, and CD8. A chest CT detected superior mediastinal masses. The physician ordered a test to assess the TCRG and TCRB gene rearrangement. The bottom panel was from a normal control, the middle from the bone marrow, and the top from the biopsy of the mass.
A.The results of the bone-marrow biopsy indicated a clonal proliferation of B cells.
B.The results of the bone-marrow biopsy indicated a clonal proliferation of T cells.
C.The results of the biopsy from the mass indicated a clonal proliferation of B cells.
D.The results of the biopsy from the mass indicated a clonal proliferation of T cells.
E.The results of both samples indicated a clonal proliferation of B cells.
F.The results of both samples indicated a clonal proliferation of T cells.
F.The results of both samples indicated a clonal proliferation of T cells.
The V domains in the TCRA and TCRG chains are assembled from V and J gene segments, whereas the TCRB and TCRD chains are assembled from V, diversity (D), and J segments.
The EuroClonality (BIOMED-2) consortium has led to standardization and has significantly improved detection of the clonality of malignant B-cell/T-cell lymphomas/leukemias. Which one of the following is the standard method for the clonal assessment?
A.PCR/capillary electrophoresis
B.PCR/Sanger sequencing
C.Next-generation sequencing (NGS)
D.Restriction-fragment–length polymorphism (RFLP)
E.Southern blotting
A.PCR/capillary electrophoresis
he TCRB assay uses three separate multiplex master mix tubes (Tubes A, B, and C), while the TCRG assay utilizes two multiplex master mix tubes (Tubes A and B).
Which one of the following statements regarding molecular T-cell receptor gene rearrangement analysis is CORRECT?
A.The TCRA gene is the most commonly tested locus.
B.The TCRB gene is the most commonly tested locus.
C.The TCRC gene is the most commonly tested locus.
D.The TCRD gene is the most commonly tested locus.
E.The TCRG gene is the most commonly tested locus.
E.The TCRG gene is the most commonly tested locus
TCRα and TCRδ on chromosome 14
TCRβ and TCRγ on chromosome 7
Which one of the following statements regarding the assessment of the clonality in the immunoglobulins or TCRs is CORRECT?
A.DNAs from paraffin-embedded tissue have higher detection rate than DNAs from bone-marrow samples.
B.“Pseudoclonality” usually happens when patients have leukocytosis.
C.Single clonal or oligoclonal results are always associated with neoplasms.
D.The sensitivity of the BIOMED-2 assay for TCRG and TCRB is more than 90%.
E.The utility of the assay is limited in the early stages of lymphomas/leukemias.
D.The sensitivity of the BIOMED-2 assay for TCRG and TCRB is more than 90%.
Which one of the following statements regarding the assessment of the clonality in the immunoglobulins (IGH and IGK) or TCRs (TCRG and TCRB) is NOT correct?
A.PCR/capillary electrophoresis works better than Southern blot for paraffin-embedded tissue.
B.PCR/capillary electrophoresis is more sensitive than Southern blot. C.PCR/capillary electrophoresis is less time consuming than Southern blot.
D.PCR/capillary electrophoresis may detect more possible clonal rearrangements than Southern blot.
E.PCR/capillary electrophoresis has a higher false positive rate than Southern blot.
D.PCR/capillary electrophoresis may detect more possible clonal rearrangements than Southern blot.
What is the difference between the immunoglobulin (IGH and IGK) and T-cell receptor (TCRG and TCRB) clonal rearrangements?
A.A developing T cell has fewer chances to productively rearrange β chains than a developing B cell has for H chains.
B.Somatic hypermutation does not generate diversity in T-cell receptors, while it does in B-cell immunoglobulin.
C.TCR loci are rearranged by the different enzymes from the immunoglobulin loci.
D.TCR has fewer rearrangements than immunoglobulin.
E.TCR rearrangements happen throughout the lifetime, while Ig rearrangements happen only before adolescence.
B.Somatic hypermutation does not generate diversity in T-cell receptors, while it does in B-cell immunoglobulin.
T-cell receptor loci have roughly the same number of V gene segments as do the immunoglobulin loci, but only B cells diversify rearranged V region genes by somatic hypermutation. Somatic hypermutation does not generate diversity in T-cell receptors.
Which immunoglobulin(s) is(are) most commonly used for the clonal assessment?
A.IGH D–J and IGK
B.IGH V–J and IGK
C.IGH V–J and IGL
D.IGH D–J and IGL
E.IGH D–J F.IGH V–J
B.IGH V–J and IGK
three different IGH V-J targets are chosen, followed by the IGK targets. of IGH V–J and IGK targets should be sufficient in the vast majority of cases (95%), evaluation of the IGH D–J and IGL targets might occasionally be helpful as a second-line approach.
The EuroClonality (BIOMED-2) consortium has led to standardization and has significantly improved detection of the clonality of malignant B-cell/T-cell lymphomas/leukemias. Which T-cell receptor (TCR) gene(s) is(are) most commonly used for the clonal assessment?
A.TCRA
B.TCRD
C.TCRD and TCRA
D.TCRB
E.TCRG
F.TCRG and TCRB
F.TCRG and TCRB
Chromosome 7
The physician ordered a test to assess the clonality in the IGH gene for a neck mass in an 80 yo. The results showed three low-amplitude peaks. The internal control, known polyclonal control, and known clonal control showed the expected results. Which one of the following would be the most appropriate next step in the workup?
A.Repeating the test with the same specimen
B.Requesting second specimen for confirmation
C.Signing the case out as positive for B cell monoclonality
D.Any of the above
E.None of the above
A.Repeating the test with the same specimen
For cases with a low percentage of suspected B or T cells, reproducibility of the profiles is essential.
The physician ordered a test to assess the clonality in the IGH gene for a neck mass in an 80 yo. The results showed three low-amplitude peaks. The internal control, known polyclonal control, and known clonal control showed the expected results. The test was repeated with the same sample, and results showed three different low-amplitude peaks. Which one of the following would be the most appropriate interpretation?
A.Presence of oligoclonal IGH populations, consistent with diagnosis of a malignancy
B.Presence of oligoclonal IGH populations, consistent with reactive clones
C.Presence of oligoclonal IGH populations, uncertain significance D.Pseudoclonality, consistent with a paucity of B cells in the sample E.Negative, no clonal IGH populations
F.Wrong sample in the second test, remedial action form needed
D.Pseudoclonality, consistent with a paucity of B cells in the sample
Posttransplantation lymphoproliferative disorder (PTLD) was suspected. To establish the cell clonality, which of the following would be the most informative assay?
A.Southern blot analysis of IGH and IGK gene rearrangement with the biopsy sample
B.Southern blot analysis of IGH and IGK gene rearrangement with the peripheral-blood sample
C.Southern blot analysis of IGH and IGK gene rearrangement with the bone-marrow sample
D.PCR/capillary electrophoresis of IGH and IGK gene rearrangement with the biopsy sample
E.PCR/capillary electrophoresis of IGH and IGK gene rearrangement with the peripheral-blood sample
F.PCR/capillary electrophoresis of IGH and IGK gene rearrangement with the bone-marrow sample
D.PCR/capillary electrophoresis of IGH and IGK gene rearrangement with the biopsy sample
A bone-marrow biopsy was obtained, and the impression was chronic myeloid leukemia (CML) with lymphoid blast crisis. Which molecular genetic test results would most likely be abnormal with this bone-marrow specimen?
A.BCR::ABL1
B.CEBPA
C.FLT3-ITD
D.FLT3-TKD
E.JAK2
F.NPM1
A.BCR::ABL1
The oncologist ordered a qualitative BCR::ABL1 test of this bone-marrow specimen to further characterize this leukemia. Which one of the following statements regarding the qualitative BCR::ABL1 test is correct?
1.It is a DNA-based test.
2.It is a RNA-based test.
3.A single PCR reaction.
4.Multiple PCR reactions.
5.It tests BCR-ABL1 fusion.
6.It tests ABL1-BCR fusion.
E.2, 4, and 5
The oncologist ordered a qualitative BCR::ABL1 test of this bone-marrow specimen to further characterize this myeloproliferative disorder. Which one of the following statements regarding the quantitative BCR::ABL1 test is NOT correct?
A.It is a DNA-based test.
B.It is a reverse transcriptase (RT-PCR) reaction.
C.There is one amplicon for the p190.
D.There are two amplicons for the p210.
E.There is one amplicon for the p230.
A.It is a DNA-based test.
How frequently do patients with chronic myelogenous leukemia (CML) have a BCR::ABL1 fusion gene?
A.95%
B.75%
C.50%
D.25%
E.<5%
A.95%
How frequently do patients with acute myeloid leukemia (AML) have a BCR::ABL1 fusion gene?
A.95%
B.75%
C.50%
D.25%
E.<5%
E.<5%
in 3% of AML and 1% of childhood AML.
How frequently do adult patients with precursor B ALL have a BCR::ABL1 fusion gene?
A.95%
B.75%
C.50%
D.25%
E.<5%
D.25%
How frequently do pediatric patients with precursor B ALL have a BCR::ABL1 fusion gene?
A.95%
B.75%
C.50%
D.25%
E.5%
E.5%
20%–30% of adults and in 5% of children.
The patient was diagnosed with pre-B acute lymphoblastic leukemia (ALL). Which one of the following isoforms of BCR::ABL1 would the patient most likely have?
A.a19b2
B.b2a2
C.b3a2
D.e1a2
E.e13a2
F.e14a2
D.e1a2
p190 = e1a2 = 50-70% of B-ALL
p210 = e13a2 (b2a2) or e14a2 (b3a2)
p230 = e19a2 (c3a2)
Which one of the following BCR::ABL1 fusions would most likely be positive if the patient had a CML with t(9;22)?
A.a19b2
B.e1a1
C.e2a2
D.e3a2
E.e14a2
F.e19a2
E.e14a2
Which one of the following BCR::ABL1 fusions would most likely be positive if the patient had a CML with t(9;22)?
A.a19b2
B.e1a1
C.e2a2
D.e3a2
E.e13a2
F.e19a2
E.e13a2
Which one of the following BCR::ABL1 fusions would most likely be positive if the patient had a CML with t(9;22)?
A.a19b2
B.b2a2
C.b13a2
D.e1a1
E.e19a2
B.b2a2
p210 = e13a2 (b2a2) or e14a2 (b3a2)
Which one of the following fusions of BCR::ABL1 would most likely be positive if the adult patient with CML had a t(9;22)?
A.a19b2
B.b3a2
C.b14a2
D.e1a1
E.e19a2
B.b3a2
Which one of the following BCR::ABL1 fusions corresponds to the p230 isoform?
A.a19b2
B.b3a2
C.e1a1
D.e13a2
E.e19a2
E.e19a2
Which one of the following BCR::ABL1 fusions corresponds to the p230 isoform?
A.a19b2
B.b3a2
C.c3a2
D.e1a1
E.e13a2
C.c3a2
p230 = e19a2 (c3a2)
Which one of the following BCR::ABL1 fusions corresponds to an isoform with the highest tyrosine kinase activity?
A.a19b2
B.b3a2
C.e1a2
D.e13a2
E.e19a2
C.e1a2
A molecular test was ordered to further assess the resistance. Which one of the following statements regarding the molecular test for imatinib resistance is correct?
A.It is a DNA-based test of the tyrosine kinase domain in the ABL1 gene.
B.It is a DNA-based test of the tyrosine kinase domain in the BCR gene.
C.It is a RNA-based test of the tyrosine kinase domain in the BCR-ABL1 gene.
D.It is a RNA-based test of the tyrosine kinase domain in the ABL1 and BCR-ABL1 genes.
E.It is a RNA-based test of the tyrosine kinase domain in the ABL1-BCR gene.
F.It is a RNA based test of the tyrosine kinase domain in the ABL1 and ABL1-BCR genes.
C.It is a RNA-based test of the tyrosine kinase domain in the BCR-ABL1 gene.
The list of amino acid substitutions detected in imatinib-resistant patients has steadily grown to >90, although some are definitely more frequent than others. Different mutations have been shown to confer variable degrees of resistance to imatinib.
T315I being the unique exception. resistant to 1st and 2nd gen ABL1 TKIs
Which one of the following malignancies most likely does NOT have an acquired BCR::ABL1 rearrangement?
A.Acute myeloid leukemia (AML)
B.Acute B lymphoblastic leukemia (B ALL)
C.Acute T lymphoblastic leukemia (T ALL)
D.Chronic lymphocytic leukemia (CLL)
E.Myeloid proliferative neoplasm (MPN)
D.Chronic lymphocytic leukemia (CLL)
A bone-marrow biopsy was obtained and the impression was chronic myeloid leukemia (CML) with lymphoid blast crisis. Chromosome karyotype analyses revealed 46,XX,t(9;22)(q34;q11.2)[6]/48,idem,+8,der(22)t(9;22)(q34;q11.2)[4]/46,XX[10]. The results of a quantitative BCR-ABL1 test were positive for p210. Which one of the following targeted therapies would be most appropriate to this patient?
A.Gleevec (imatinib)
B.Herceptin (trastuzumab)
C.Lynparza (olaparib)
D.Zelboraf (vemurafenib)
E.None of the above
A.Gleevec (imatinib)
CML with EB. Which one of the following molecular tests would be appropriate for this patient in order to assist in the decision about future therapy?
A.FISH
B.PCR-capillary electrophoresis
C.Sanger sequencing
D.Targeted-mutation analysis
E.All of the above
F.None of the above
A.FISH
BCR::ABL1
One year later the patient had reappearance of BCR::ABL1 p210, even though she had been taking Gleevec (imatinib) as her doctor suggested. The follow-up karyotype results were 46,XX,t(9;22)(q34;q11.2)[12]/46,XX[8]. Which one of the following molecular tests would be appropriate for this patient in order to assistant in the decision about future therapy?
A.Detect amplification of ABL1/BCR rearrangement
B.Detect amplification of BCR/ABL1 rearrangement
C.Detect deletion of BCR/ABL1 rearrangement
D.Identify BCR/ABL1 kinase domain mutation in the ABL1 gene E.Identify BCR/ABL1 kinase domain mutation in the BCR gene F.None of the above
D.Identify BCR/ABL1 kinase domain mutation in the ABL1 gene
BALL with 90% blasts in BM and 2% PB. B cell flow with TdT+, MPO- and CD34+. Qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) test for BCR-ABL1 was ordered, and the result was positive for p190. For which one of the following BCR::ABL1 fusion types would this patient most likely be positive in this specimen?
A.p190
B.p205
C.p210
D.p230
E.All of the above
F.None of the above
A.p190
A qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) test for BCR::ABL1 was ordered, and the result was positive for p190. Which one of the following prognoses would this patient most likely have?
A.Favorable risk
B.Intermediate risk
C.Unfavorable risk
D.Unclear
E.None of the above
C.Unfavorable risk
The p190 protein has an increased tyrosine kinase activity compared with p210 and is associated with a more aggressive leukemia. In both children and adults, t(9;22) ALL has the worst prognosis among patients with ALL.
The oncologist suspected that the patient had primary myelofibrosis (PMF). Which one of the following molecular assays would most likely be ordered to confirm the diagnosis in this patient?
A.BCR-ABL1 qualitative test
B.CALR exon 9 mutation
C.JAK2 exon 12 mutation
D.JAK2 V617F mutation
E.MPL exon 10 mutation
D.JAK2 V617F mutation
A qualitative molecular test demonstrated the JAK2 V617F mutation. Which one of the following conditions would the patient most likely NOT have?
A.Chronic myeloid leukemia (CML)
B.Essential thrombocythemia (ET)
C.Polycythemia vera (PV)
D.Primary myelofibrosis (PMF)
E.None of the above
A.Chronic myeloid leukemia (CML)
The oncologist suspected that the patient had primary myelofibrosis (PMF). A qualitative molecular test demonstrated the presence of the JAK2 V617F mutation. Which one of the following genetic assays would most likely also be positive in this patient?
A.BCR-ABL1 rearrangement
B.CALR exon 9 mutation
C.JAK2 exon 12 mutation
D.MPL exon 10 mutation
E.None of the above
E.None of the above
JAK2 V617F is exon 14,
Over 50 different mutations have now been reported within exons 12 through 15 of JAK2, and essentially all of the non-V617F mutations have been identified in PV.
58 yo white-blood-cell count was 8×103cells/mm3, with an absolute neutrophil count of 1400cells/mm3, hemoglobin 9.3g/dL, and platelet count 76,000cells/mm3. A bone marrow biopsy resulted in a “dry” aspirate, and the core biopsy was markedly fibrotic. An estimate of the blast count based upon touch preps as well as a CD34+/CD117+ immunostaining of the core biopsy demonstrated only 1.2% blasts. A qualitative molecular test demonstrated the absence of the JAK2 V617F mutation. Which one of the following conditions would be ruled out in this patient if the JAK2 V617F molecular test was negative?
A.Chronic myeloid leukemia (CML)
B.Essential thrombocythemia (ET)
C.Polycythemia vera (PV)
D.Primary myelofibrosis (PMF)
E.None of the above
E.None of the above
(MPNs), such as polycythemia vera (PV; close to 100%), essential thrombocythemia (ET; approximately 50%), and primary myelofibrosis (PMF; approximately 50%),
CALR exon 9 mutations (20%–30% of PMF and ET) and MPL exon 10 mutation (5%–10% of PMF and 3%–5% of ET). Mutations in JAK2, CALR, and MPL are essentially mutually exclusive.
A qualitative molecular test did not detect the JAK2 V617F mutation. But the physician still suspected that the patient had primary myelofibrosis (PMF). Which one of the following molecular genetic tests would be helpful in order to further establish/rule out the diagnosis of PMF in this patient?
A.BCR-ABL1 rearrangement
B.CALR exon 9 mutation
C.JAK2 exon 12 mutation
D.All of the above
E.None of the above
B.CALR exon 9 mutation
CALR exon 9 mutations were found in 20%–30% of PMF and ET. MPL exon 10 mutations were found in 5%–10% of PMF and 3%–5% of ET.
A physical examination revealed bruising on the extremities, and palpation of the spleen showed slight splenomegaly. A complete blood count revealed WBCs 12.1×109/L, RBCs 3200×109/L, Hgb 9g/dL, Hct 34%, platelet count 250×109/L, and blasts 0%. A bone-marrow biopsy revealed fibrosis. The karyotype results of the bone marrow showed 46,XX[20]. A qualitative molecular test detected the JAK2 V617F mutation. Which one of the following statements would be most appropriate for this patient?
A.The presence of the JAK2 V617F mutation rules out the diagnosis of chronic myeloid leukemia (CML).
B.The presence of the JAK2 V617F mutation establishes the diagnosis of essential thrombocythemia (ET).
C.The presence of the JAK2 V617F mutation establishes the diagnosis of polycythemia vera (PV).
D.The presence of the JAK2 V617F mutation establishes the diagnosis of primary myelofibrosis (PMF).
E.None of the above.
A.The presence of the JAK2 V617F mutation rules out the diagnosis of chronic myeloid leukemia (CML).
The oncologist suspected that the patient had primary myelofibrosis (PMF). A qualitative molecular test did not detect the JAK2 V617F mutation. The oncologist still suspected that the patient had primary myelofibrosis (PMF). Which one of the following molecular genetic tests would be helpful in order to establish the diagnosis in this patient?
A.BCR-ABL1 rearrangement
B.JAK2 exon 12 mutation
C.MPL exon 10 mutation
D.All of the above
E.None of the above
C.MPL exon 10 mutation
A qualitative molecular test did not detect the JAK2 V617F mutation. A reflex molecular test was ordered in order to further confirm/rule out myeloproliferative neoplasm (MPNs). Which one of the following mutations would NOT be part of this reflex test for MPNs in this patient?
A.FLT3-ITD mutation
B.JAK2 T875N mutation
C.MPL W515 mutation
D.MPL S505N mutation
E.None of the above
A.FLT3-ITD mutation
A qualitative molecular test did not detect the JAK2 V617F mutation. A reflex molecular test was ordered in order to further confirm/rule out myeloproliferative neoplasm (MPNs) in this patient, and a mutation in the CALR gene was detected. Which one of the following exons of the CALR gene would the detected mutation most likely be located in this patient?
A.Exon 9
B.Exon 10
C.Exon 12
D.Exon 18
E.Exon 19
A.Exon 9
out-of-frame insertions and/or deletions (in/dels) in exon 9, generating a frame shift and a mutant protein with a novel C-terminus rich in basic amino acids and loss of the KDEL ER-retention signal. The most common mutation types are 52-bp deletion (c.1092_1143del, L367fs46) and 5-bp insertion (c.1154_1155insTTGCC, K385fs47), and they comprise approximately 85% of CALR mutations in MPN. CALR mutations have been found in hematopoietic stem and progenitor cells in MPN patients and may activate the STAT5 signaling pathway. They are associated with a decreased risk of thrombosis in ET, and better survival in PMF compared to JAK2 mutations.
And a mutation in the exon 9 of the CALR gene was detected. Which one of the following types of mutations in CALR would most likely be detected in this patient?
A.In-frame deletion/insertion
B.Out–of-frame deletion/insertion
C.Single-nucleotide mutation
D.Translocation
E.None of the above
B.Out–of-frame deletion/insertion
52-bp deletion (L367fs46) and a 5-bp insertion (K385fs47)
The oncologist suspected that the patient had primary myelofibrosis (PMF). A qualitative molecular test did not detect the JAK2 V617F mutation. A reflex molecular test was ordered in order to further confirm/rule out myeloproliferative neoplasm (MPNs) in this patient. And a mutation in the exon 9 of the CALR gene was detected. Which one of the following describes the prognostic significance of the mutation detected in the CALR gene for this patient?
A.Favorable prognosis
B.Intermediate prognosis
C.Unfavorable prognosis
D.Better survival than JAK2 mutations
E.Worse survival than JAK2 mutations
F.Unclear
G.None of above
D.Better survival than JAK2 mutations
A peripheral-blood specimen was collected for a qualitative JAK2 V617F mutation analysis, and the results were positive. Which one of the following conditions most likely has JAK2 V617F?
A.Chronic myeloid leukemia (CML)
B.Essential thrombocythemia (ET)
C.Polycythemia vera (PV)
D.Primary myelofibrosis (PMF)
E.None of the above
C.Polycythemia vera (PV)
polycythemia vera (PV; close to 100%), essential thrombocythemia (ET’ approximately 50%), and primary myelofibrosis (PMF; approximately 50%)
essentially never in CML
Which one of the following molecular abnormalities would this patient most likely have if he had PV?
A.BCR-ABL1 rearrangement
B.CALR mutation
C.JAK2 V617F mutation
D.JAK2 mutation in the exon 12
E.MPL mutation
C.JAK2 V617F mutation
A peripheral-blood specimen was collected for a qualitative JAK2 V617F mutation analysis, and the results were negative. A reflex molecular test was ordered to further confirm/rule out PV in this patient. Which one of the following analyses would most likely be part of this reflex test for this patient with PV?
A.CALR exon 9 mutation
B.JAK2 exon 12 mutation
C.MPL exon 10 mutation
D.All of the above
E.None of the above
B.JAK2 exon 12 mutation
JAK2 V617F (exon 14)
CALR exon 9 mutations (20%–30% of PMF and ET) and MPL exon 10 mutation (5%–10% of PMF and 3%–5% of ET).
A peripheral-blood specimen was collected for a qualitative JAK2 V617F mutation analysis, and the results were positive. Which one of the following targeted therapies would be most appropriate to this patient?
A.Gleevec (imatinib)
B.Herceptin (trastuzumab)
C.Lynparza (olaparib)
D.Zelboraf (vemurafenib)
E.None of the above
E.None of the above
ruxolitinib (Jakafi)
A quantitative laboratory assay specific for the JAK2 V617F allele was ordered. The results showed 65% JAK2 V617F in the peripheral-blood sample. Which one of the following statements would be the most appropriate explanation for this finding?
A.All the cancer cells in the sample are heterozygous for the JAK2 V617F mutation.
B.All the cancer cells in the sample are homozygous for the JAK2 V617F mutation.
C.At least some of the cancer cells in the sample are homozygous for the JAK2 V617F mutation.
D.At least some of the cancer cells in the sample are heterozygous for the JAK2 V617F mutation.
E.The result is positive, however, it is not possible to predict the zygosity of the sample.
C.At least some of the cancer cells in the sample are homozygous for the JAK2 V617F mutation.
A quantitative laboratory assay specific for the JAK2 V617F allele was ordered. The results were 80% V617F allele, which suggested that the patient was homozygous for the JAK2 V617K mutation in at least a subset of cells. What would be the most likely explanation for the homozygous JAK2 mutation in this patient?
A.Both copies of JAK2 in some cells were mutated to V617F; this fits the two-hit hypotheses.
B.The patient had one inherited copy of the mutation and one somatic mutation.
C.This is a laboratory error.
D.This may be copy neutral loss of heterozygosity (LOH) due to uniparental disomy (UPD).
E.All of the above.
F.None of the above.
D.This may be copy neutral loss of heterozygosity (LOH)
Which one of the following statements regarding the quantitative JAK2 V617F test is correct?
A.It is a DNA-based test.
B.It is a RNA-based test.
C.It is multiple PCR reactions.
D.The recommended test sensitivity is 0.1%.
E.The recommended test sensitivity is 5%.
A.It is a DNA-based test.
A peripheral-blood specimen was collected for quantitative JAK2 V617F mutation analysis, and the result was positive. How frequently is the JAK2 V617F mutation found in patients with polycythemia vera (PV)?
A.About 3%
B.About 20%
C.About 60%
D.About 80%
E.About 95%
E.About 95%
How frequently is the JAK2 V617F mutation found in patients with essential thrombocythemia (ET)?
A.About 3%
B.About 20%
C.About 60%
D.About 80%
E.About 95%
C.About 60%
How frequently is the JAK2 V617F mutation found in patients with primary myelofibrosis (PMF)?
A. About 3%
B. About 22%
C. About 60%
D. About 80%
E. About 95%
C. About 60%
How frequently are the JAK2 exon 12 mutations found in patients with polycythemia vera (PV)?
A. About 3%
B. About 20%
C. About 60%
D. About 80%
E. About 95%
A. About 3%
analysis. The results were 80% V617F allele. What would be the pathogenetic role of JAK2 V617F in this patient’s PV?
A. Activating mutations
B. Dominant negative mutations
C. Gain-of-function mutations
D. Loss-of-function mutations
E. Silent mutations
A. Activating mutations
The oncologist suspected that she had essential thrombocythemia (ET). Which one of the following genetic test results would most likely be positive if the patient had ET?
A. BCR-ABL1 FISH
B.CALR exon 9 mutation analysis
C.JAK2 exon 12 mutation analysis
D.JAK2 V617F mutation analysis
E.MPL exon 10 mutation analysis
F.None of the above
D.JAK2 V617F mutation analysis
Her JAK2 V617F and BCR-ABL1 test results were negative. A reflex molecular test was ordered to further confirm/rule out ET in this patient. Which one of the following mutations would most likely NOT be part of this reflex test for MPNs?
A.CALR exon 9 mutation analysis
B.JAK2 exon 12 mutation analysis
C.MPL exon 10 mutation analysis
D.All of the above
E.None of the above
B.JAK2 exon 12 mutation analysis
Her JAK2 V617F and BCR-ABL1 test results were negative. A reflex molecular test was ordered to further confirm/rule out ET in this patient, and a mutation in the MPL gene was detected. In which one of the following exons of the MPL gene would the mutation most likely be located?
A. Exon 9
B. Exon 10
C. Exon 12
D. Exon 18
E. Exon 19
B. Exon 10
JAK2 V617F and BCR-ABL1 test results were negative. A reflex molecular test was ordered to further confirm/rule out ET in this patient, and a mutation in the MPL gene was detected. Which one of the following types of mutation in MPL would most likely be detected in this patient?
A. In-frame deletion/insertion
B. Out-of-frame deletion/insertion
C. Single-nucleotide mutation
D. Translocation
E.None of the above
C. Single-nucleotide mutation
Her JAK2 V617F and BCR-ABL1 test results were ordered, but both turned out to be negative. What is the required analytic sensitivity of an assay to ensure that 90% of JAK2 V617F–positive cases are detected?
A. At least 0.1%
B. At least 1%
C. At least 5%
D. At least 10%
E. At least 15%
B. At least 1%
Traditionally clinical molecular laboratories have been using Sanger sequencing, restriction-fragment–length polymorphism (RFLP), denaturing high-performance liquid chromatography (dHPLC), high-resolution melting curve analysis, pyrosequencing, and various allele-specific PCR systems with electrophoretic analysis of the products to detect JAK2 V617F qualitatively. What sensitivity may these methods most likely reach?
A. 0.1%
B. 1%
C. 5%
D. 10%
E. 15%
C. 5%
With which one of the following malignancies are the FLT3-ITD and FLT3-TKD mutations associated?
A.Acute myeloid leukemia (AML)
B. Essential thrombocytopenia (ET)
C. Myeloproliferative neoplasm (MPN)
D. Polycythemia vera (PV)
E. Primary myelofibrosis (PMF)
F.None of the above
A.Acute myeloid leukemia (AML)
A bone-marrow biopsy was consistent with poorly differentiated acute myeloid leukemia (AML). The karyotype results on a bone-marrow sample were normal. Which one of the following prognoses would this patient have?
A. Favorable risk
B. Intermediate risk
C. Unfavorable risk
D. Unclear
E. None of the above
B. Intermediate risk
A next-generation sequencing (NGS) panel for acute myeloid leukemia (AML) was ordered. Which one of the following genes would most likely NOT be included in this NGS panel?
A. CEBPA
B. FLT3
C. MPL
D. NPM1
E.None of the above
C. MPL
A next-generation sequencing (NGS) panel for acute myeloid leukemia (AML) was ordered, which included the CEBPA, c-KIT, DNMT3A, FLT3, NPM1, and RUNX1, WT1 genes, and others. Which one of the following genes in the NGS panel is intronless?19 A. CEBPA
B. c-KIT
C. DNMT3A
D. FLT3
E. NPM1
F. RUNX1
G. WT1
H.None of the above
A. CEBPA
Which one of the following prognoses would this patient have if she had the FLT3-ITD mutation?
A. Favorable risk
B. Intermediate risk
C. Unfavorable risk
D. Unclear
E.None of the above
C. Unfavorable risk
Which one of the following assays would most likely be used to detect FLT3-ITD in this patient?
A.Fluorescence in situ hybridization (FISH)
B. PCR-capillary electrophoresis
C. Sanger sequencing
D. Targeted-mutation analysis
E.All of the above
F.None of the above
B. PCR-capillary electrophoresis
The FLT3-ITD mutation was detected. What would be the pathogenetic role of the FLT3-ITD mutation in this patient?
A. Activating mutations
B. Dominant negative mutations
C. Gain-of-function mutations
D. Loss-of-function mutations
E. Unclear
F.None of the above
A. Activating mutations
With which one of the following malignancies are mutations in the CEBPA gene associated?
A.Acute myeloid leukemia (AML)
B. Essential thrombocytopenia (ET)
C. Myeloproliferative neoplasm (MPN)
D. Polycythemia vera (PV)
E. Primary myelofibrosis (PMF)
F.None of the above
A.Acute myeloid leukemia (AML)
Which one of the following genes in the NGS panel would be associated with a favorable prognosis if the patient had acquired pathogenic variant(s) of it?
A. Double CEBPA mutations
B. Single CEBPA mutation
C. FLT3-ITD
D. FLT3-TKD
E. RUNX1
F. WT1
G. TP53
H.None of the above
A. Double CEBPA mutations
Which one of the following genes in the NGS panel is associated with familial acute myeloid leukemia (AML)?
A. CEBPA
B. c-KIT
C. DNMT3A
D. FLT3
E. NPM1
F. RUNX1
G. WT1
H.None of the above
A. CEBPA
The oncologist ordered molecular tests on CEBPA, FLT3-ITD, FLT3-TKD, and NPM1. Which one of the following assays would most likely be used to detect the CEBPA gene in this patient?
A. FISH
B. PCR-capillary electrophoresis
C. Sanger sequencing
D. Targeted-mutation analysis
E.All of the above
F.None of the above
C. Sanger sequencing
Acquired pathogenic mutations are heterogeneous, and more than 50 mutations have been detected in the full length of the gene.
There were two compound heterozygous mutations in the CEBPA gene. Both of them were frameshift mutations, leading to premature termination of amino acids. One was in exon 3, another one was in exon 22. Which one of the following statements regarding these findings would be the most appropriate?
A.These two mutations are in cis.
B.These two mutations are in trans.
C.It is unclear whether these two mutations are in cis or trans.
D.NGS can help to tell if these two mutations are in cis or trans.
E.No further tests can help to tell if these two mutations are in cis or trans.
C.It is unclear whether these two mutations are in cis or trans.
Unless two pathogenic mutations are in the same amplicon, it is hard to tell whether they are in cis or trans. If we are talking about germline pathogenic variants in autosomal recessive disorders, parental testing is helpful to distinguish in cis from in trans variants.
Which one of the following statements regarding CEBPA in leukemia is NOT correct? A.Acquired mutations in CEBPA are recurrent genetic alterations in AML.
B.Acquired mutations in CEBPA are often biallelic in AML.
C.Biallelic CEBPA mutations are associated with a favorable prognosis.
D.The CEBPA gene is an intronless gene.
E.The prognostic impact of CEBPA mutations in the presence of FLT3 mutations is unfavorable.
E.The prognostic impact of CEBPA mutations in the presence of FLT3 mutations is unfavorable.
The prognostic impact of CEBPA mutations in the presence of FLT3 mutations is unclear.
A scientist in a clinical molecular laboratory decided to validate an assay for the CEBPA gene. Which one of the following diseases has indications for CEBPA sequence analysis?
A.Acute promyelocytic leukemia (APL)
B.Chronic myelocytic leukemia (CML)
C.Complex karyotype AML raised from myeloid dysplastic syndrome (MDS) D.Normal karyotype with acute myeloid leukemia (AML)
E.Normal karyotype AML with a FLT3-ITD mutation
D.Normal karyotype with acute myeloid leukemia (AML)
10%–18% of individuals with cytogenetically normal acute myeloid leukemia (AML).
The N-terminal mutations of CEBPA lead to overexpress the 30-kD isoform of the CEBPA protein, which typically are which one of the following?
A. Activating mutations
B. Dominant negative mutations
C. Gain-of-function mutations
D. Loss-of-function mutations
E. Silent mutations
B. Dominant negative mutations
Which one of the following statements regarding CEBPA in leukemia is correct?
A.The most common mutations in CEBPA are N-terminal frameshift and C-terminal in-frame mutations.
B.The most common mutations in CEBPA are N-terminal in-frame and C-terminal frameshift mutations.
C.Dysregulation of CEBPA has been identified only in AML.
D.Patients with monoallelic CEBPA mutations have a poor prognosis.
E.Patients with monoallelic CEBPA mutations, but not biallelic CEBPA mutations, have a favorable prognosis.
A.The most common mutations in CEBPA are N-terminal frameshift and C-terminal in-frame mutations.
An acquired pathogenic mutation in the NPM1 gene was detected. Which one of the following prognoses would the patient most likely have, according to the genetic findings?
A. Favorable risk
B. Intermediate risk
C. Unfavorable risk
D. Unclear
E.None of the above
A. Favorable risk
Which one of the following types of mutation in NPM1 would most likely be detected in this patient?
A. In-frame deletion/insertion
B. Out-of-frame deletion/insertion
C. Single-nucleotide mutation
D. Translocation
E.None of the above
B. Out-of-frame deletion/insertion
4 bp insertion - type A TCTG
Which one of the following assays would most likely be used to test the NPM1 gene in this patient?
A. FISH
B. PCR-capillary electrophoresis
C. Sanger sequencing
D. Targeted-mutation analysis
E.All of the above
F.None of the above
B. PCR-capillary electrophoresis
exon 12 of the NPM1 gene. This AML type frequently has myelomonocytic or monocytic features and typically presents de novo in older adults with a normal karyotype. The majority of mutations in the NPM1 gene are 4-bp insertions.
Which one of the following statements describes the limitation of the utility of Sanger sequencing in oncology?
A.It is not a sensitive test to detect acquired mutations.
B.It cannot be used to detect large deletions or insertions.
C.It does not help to monitor minimal residue diseases (MRDs).
D.It cannot be used to tell whether compound heterozygous mutations in CEBPA are in cis or in trans.
E.All of the above
F.None of the above
E.All of the above
Which one of the following genes associated with myeloid neoplasms does NOT have a tyrosine kinase domain or domains?
A. ABL1
B. FLT3
C. JAK2
D. KIT
E. NPM1
E. NPM1
AML patient. Which one of the following genetic alterations would indicate the patient had a favorable prognosis if he had acquired pathogenic variant(s) in this gene?
A. BAALC
B. ERG1
C. FLT3-ITD
D. MLL-PTD
E. MN1
F. NPM1
F. NPM1
AML patient. Which one the following genetic alterations would indicate that the patient had an unfavorable prognosis, if he had one?
A. CEBPA
B. FLT3-ITD
C. FLT3-TKD
D. NPM1
B. FLT3-ITD
A diagnosis of myelodysplastic syndrome (MDS) was made. Chromosome karyotype results were normal. A next-generation sequencing (NGS) panel for MDS was ordered to further assess the prognosis. An acquired pathogenic variant in the SF3B1 gene was detected. Which one of the following prognoses would this patient most likely have?
A. Favorable risk
B. Intermediate risk
C. Unfavorable risk
D. Unclear
E.None of the above
A. Favorable risk
The ASXL1 gene is an epigenetic regulator of gene expression. Acquired pathogenic variants of ASXL1 are detected in approximately 15% of cases of MDS, 11% of AML, 45% of CMML, 30% of PMF, and 4% of PV/ET and are generally associated with aggressive and poor outcome in these conditions. Which one of the exons in this gene most likely harbors an acquired pathogenic variant in a patient with a myeloid malignancy?
A. Exon 2
B. Exon 9
C. Exon 10
D. Exon 13
E.All of the above
F.None of the above
D. Exon 13
Most ASXL1 mutations occur in exon 13 (referred to as exon 12 in many publications)
The oncologist ordered MLL-partial tandem duplication (PTD) analysis. Which one of the following assays would most likely be used for the MLL-PTD analysis in this patient?
A. A DNA-detecting assay
B. An RNA-detecting assay
C. Sequencing
D. Multiple PCR
E.All of the above
F.None of the above
B. An RNA-detecting assay
MLL has been found in >51 different translocations with distinct fusion partners.
Research showed that in some patients with acute myeloid leukemia (AML), MLL is not fused with a partner gene but rather is consistently elongated with a partial tandem duplication (PTD) of exons 11-5 or 12-5 (former exon designations were 6-2 and 8-2). Leukemia-cell RNA with the MLL-PTD can be detected with RT-PCR using primers that flank the duplication repeat.
The oncologist ordered MLL-partial tandem duplication (PTD) analysis, and the results were abnormal. Which one of the following types of changes would this patient most likely have?
A. In-frame duplication
B. Out-of-frame duplication
C. Single-nucleotide mutation
D. Translocation
E.None of the above
A. In-frame duplication
mixed lineage leukemia gene (MLL), located on 11q23, was initially recognized as a recurrent locus of chromosomal translocation in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL).
A scientist in a clinical molecular laboratory was developing a next-generation sequencing (NGS) panel for acute myeloid leukemia (AML). Which one of genetic alterations would most likely NOT be included in this NGS panel for AML?
A. CALR
B. CEBPA
C. FLT3-ITD
D. MLL-PTD
E. NPM1
F.None of the above
A. CALR
A scientist was developing a next-generation sequencing (NGS) panel for acute myeloid leukemia (AML). Which one of genetic alterations would most like NOT be included in this NGS panel for AML?
A. ASXL1
B. CEBPA
C. MPL
D. RUNX1
E. SF3B1
F.None of the above
C. MPL
exon 10 of the MPL gene are in approximately 5% of patients with primary myelofibrosis (PMF) and essential thrombocythemia (ET),
fever. Results of a bone-marrow biopsy were consistent with acute myeloid leukemia (AML). Most AML cells were MPO+, CD20 partial +, CD79a partial+, CD3 partial+, some CD138+, CD−, CD5−, Ag+, and Fe+. Cytogenetic karyotype results were 47,XX,+8[9]/46,XX[11]. Which one of the following genes in the NGS panel would most likely be mutated in this patient?
A. ASXL1
B. CEBPA
C. GATA1
D. GATA2
E. SF3B1
F.All of the above
G.None of the above
A. ASXL1
Trisomy 8 is one of the most frequent cytogenetically gained aberrations in acute myeloid leukemia (AML). Patients with isolated trisomy 8 (tri 8) are usually older, male, present with lower WBC counts, and more often harbor acquired pathogenic variants in the ASXL1, and RUNX1 genes but less frequently FLT3-ITD, NPM1 mutations, or double-mutated CEBPA
An acquired pathogenic variant in the ASXL1 gene was detected. Which one of the following prognoses would this patient most likely have?
A. Favorable risk
B. Intermediate risk
C. Unfavorable risk
D. Unclear
E.None of the above
C. Unfavorable risk
Trisomy 8 associated with ASXL1 and RUNX1 mutations
ASXL1 exon 12 mutations are frequent in AML with an intermediate-risk karyotype and are independently associated with an adverse outcome.
Therefore, it would most likely that this patient had an unfavorable risk, since he had an acquired pathogenic variant in the ASXL1 gene with trisomy 8.
A scientist in a clinical molecular laboratory decided to develop a next-generation sequencing (NGS) panel for acute myeloid leukemia (AML) including the RUNX1 (AML1) gene. Which one of the following aberrations in the RUNX1 gene is NOT a recurrent one in patients with AML?
A.Amplification
B.Deletion
C.Point mutation
D.Translocation
E.None of the above
E.None of the above
21q22.12
transcription factor that regulates the differentiation of hematopoietic stem cells into mature blood cells. It is unclear whether RUNX1 is a proto-oncogene or tumor suppressor gene.
RUNX1T1/RUNX1 due to t(8;21)(q21.3;q22.12)
RUNX1 is also oncogenic when overexpressed.
An acquired pathogenic variant in the KIT gene was detected. In which one of the exons would the KIT mutation most likely be located in this AML patient?
A.Exon 8
B.Exon 11
C.Exon 13
D.Exon 17
E.None of the above
D.Exon 17
KIT is mutated in 8.0% of AML. And KIT mutations primarily occur in exon 17 and affect the activation loop of the kinase domain. Some of KIT mutations occur in exon 8 (1.8%).
Approximately 80% of GISTs harbor a mutation in KIT gene, while 2%–5% harbor mutations in PDGFRA. In GIST, somatic mutations within the KIT gene are located in exons 2, 9, 10, 11, 13, 14, 15, 17, and 18, and somatic mutations within the PDGFRA gene are located in exons 12, 14, 15, and 18.
A 2-day-old male was born at 36 weeks’ gestation with a prenatal diagnosis of constitutional trisomy 21. A complete blood count was notable for white-blood-cell count (WBC) 129×103/µL, hematocrit 36.4%, platelet count 119×103/µL, and 10%–15% blasts. During the next 3 weeks the WBC count normalized and blasts disappeared from circulation. Which one of the following genetic alterations would most likely be detected in this patient’s peripheral-blood sample when his WBC was high?
A.CALR
B.GATA1
C.GATA2
D.NPM1
E.RUNX1
F.None of the above
B.GATA1
10- to 100-fold and extends into the adult years. Approximately 10% of Down syndrome neonates manifest transient abnormal myelopoiesis (TAM). In 20%–30% of the affected cases, nonremitting acute megakaryoblastic leukemia subsequently develops in 1–3 years.
also have an increased incidence of acute lymphoblastic leukemia (ALL).
TAM patient with trisomy 21. Molecular analyses of the GATA1 gene were ordered. Which one of the following locations in the GATA1 gene would most likely harbor a pathogenic variant in this patient?
A.Exon 1
B.Exon 2
C.Exon 3
D.Exon 4
E.Exon 5
F.None of the above
B.Exon 2
fs or nonsense
Molecular analyses of the GATA1 gene were ordered. Which one of the following assays would most likely be used for the GATA1 gene in this patient?
A.FISH
B.PCR-capillary electrophoresis
C.Sanger sequencing
D.Targeted-mutation analysis
E.All of the above
F.None of the above
C.Sanger sequencing
An acquired pathogenic variant in the RUNX1 gene was detected. Which one of the following prognoses would this patient most likely have, based on the NGS results?
A.Favorable risk
B.Intermediate risk
C.Unfavorable risk
D.Unclear
E.None of the above
C.Unfavorable risk
Patient with pancytopenia. Family with MDS. BMBx showed megakaryocytic atypia and erythroid dysplasia. The hematologist suspected that the patient had a hereditary condition and ordered a molecular test to confirm the suspicion. Which one of the following genes would most likely be tested in this patient for the hereditary condition?
A.ASXL1
B.GATA1
C.GATA2
D.RUNX1
E.RUNX2
F.SF3B1
G.All of the above
H.None of the above
C.GATA2
myelodysplastic syndrome (MDS) associated with GATA2 deficiency syndrome. Haploinsufficiency in the GATA2 gene leads to a wide range of hematologic consequences, including aplastic anemia, chronic neutropenia, and an increased risk of developing MDS or acute myeloid leukemia (AML).
low or absent B cells, T cells, and natural killer cells. Recurrent herpes infections, lymphedema, and atypical mycobacterial infections are common in GATA2 deficiency syndromes.
The hematologist suspected that the patient had a hereditary condition and ordered a molecular test to confirm the suspicion. A germline pathogenic variant in the GATA2 gene was detected. Which one of the following genes would likely be somatically mutated in this patient?
A.ASXL1
B.GATA1
C.RUNX1
D.RUNX2
E.SF3B1
F.All of the above
G.None of the above
A.ASXL1
Approximately 30% of patients with hereditary GATA2 deficiency syndrome have an acquired heterozygous pathogenic variant in the ASXL1 gene.
The patient was subsequently diagnosed with pre-B acute lymphoblastic leukemia (ALL). Which one of the following BCR-ABL1 fusions would the patient most likely have?
A.p190
B.p205
C.p210
D.p230
E.All of the above
F.None of the above
A.p190
25% of adult ALL cases, and 3%–5% of pediatric ALL cases.
FISH analyses for BCR-ABL1 were positive. The patient was subsequently diagnosed with pre-B acute lymphoblastic leukemia (ALL). Which one of the following prognoses would this patient most likely have?
A.Favorable risk
B.Intermediate risk
C.Unfavorable risk
D.Unclear
E.None of the above
C.Unfavorable risk
A diagnosis of hairy-cell leukemia was made. Which one of the following genes would most likely be mutated in this patient?
A.ASXL1
B.BRAF
C.GATA2
D.RUNX2
E.SF3B1
F.None of above
B.BRAF
B-cell markers CD20, CD25, CD11c, and CD103, but not CD21 (late-B-cell marker). These cells have also been distinguished by expression of CD123 and bright annexin A1-positive cells.
BRAF V600E mutation was identified in 100% of patients with hairy-cell leukemia, and not in other lymphoproliferative disorders.
IHC stains demonstrated that the tumor cells were positive for CD30 and ALK and were distributed in a sinusoidal pattern in the bone marrow. These cells were negative for CD20, CD3, CD8, and EBER (EBV ISH stain). Which one of the following genetic alterations would this patient most likely have?
A.ALK point mutations
B.ALK amplification
C.inv(2)(p21p23) with EML4-ALK fusion
D.t(2;5)(p23;q35) with NPM1-ALK fusion
E.All of the above
F.None of the above
D.t(2;5)(p23;q35) with NPM1-ALK fusion
Which one of the following statements regarding bone-marrow engraftment in molecular analyses is correct?
A.Only the posttransplantation sample is required for the analysis.
B.Chimerism status was usually assessed on bone-marrow samples collected after transplantation. C.Sanger sequencing is the gold standard method for chimerism status analysis.
D.NGS sequencing has replaced Sanger sequencing as the first-line test for chimerism status analysis.
E.The analytical sensitivity of the chimerism status analysis is about 1%–10%.
E.The analytical sensitivity of the chimerism status analysis is about 1%–10%.
Which one of the following statements regarding bone-marrow engraftment molecular analyses is NOT correct?
A.Choose recipient-specific alleles at least two repeats smaller than the donor alleles if the recipient allele is smaller.
B.It is preferred that both donor and recipient alleles are informative.
C.The chimerism analysis may be used as an indicator for relapse.
D.The chimerism analysis can be used for autologous hematopoietic-cell transplantation.
E.Stutter peaks detected in STR analysis are caused mainly by slippage of Taq polymerase during PCR amplification of STR loci.
D.The chimerism analysis can be used for autologous hematopoietic-cell transplantation.
*Confirmation of initial engraftment following hematopoietic stem-cell transplantation (HSCT), *Monitoring of hematopoietic reconstitution by donor derived cells,
*Measurement of chimerism in cellular subpopulations to predict graft rejection, GCHD (graft versus host disease) and early relapse,
*Monitoring effectiveness of posttransplantation therapies,
*Indicator of relapse.
How frequently do patients with Burkitt lymphoma have c-MYC translocations?
A.90%
B.75%
C.50%
D.25%
E.<5%
A.90%
How frequently do patients with diffuse large-B-cell lymphoma (DLBCL) have c-MYC translocations?
A.90%
B.75%
C.50%
D.25%
E.10%
E.10%
Clinically significant mutations of EGFR are typically:
A.Activating mutations
B.Dominant negative mutations
C.Gain-of-function mutations
D.Loss-of-function mutations
E.Silent mutations
A.Activating mutations
Somatic activating mutations in exons 18–21 of the EGFR gene,
Genetic alterations in which one of the following is most prevalent in nonsmoking patients with nonsmall-cell lung cancer (NSCLC) in the United States?
A.ALK
B.BRAF
C.EGFR
D.KRAS
E.NRAS
C.EGFR
EGFR mutations are more prevalent in females (43.7%) compared to males (24.0%). They are also more common in non-smokers (49.3%) compared to smokers (21.5%).
60%–80% of Asian patients who never smoked with lung cancer.
Exon 19 deletions are the most common type, with a prevalence of around 44%, followed by L858R mutations with a prevalence of around 41%
How frequently do patients with nonsmall-cell lung cancer (NSCLC) have EGFR mutations in Western populations?
A.<1%
B.10%
C.25%
D.50%
E.75%
B.10%
How frequently do nonsmokers with nonsmall-cell lung cancer (NSCLC) have EGFR mutations in the United States?
A.<1%
B.10%
C.25%
D.50%
E.75%
D.50%
Which one of the following mutations in EGFR most likely is associated with acquired resistance to EGFR tyrosine kinase inhibitor (TKI) therapy in patients with nonsmall-cell lung cancer (NSCLC)?
A.G719X in exon 18
B.Deletions in exon 19
C.T790M in exon 20
D.L858R in exon 21
E.None of the above
C.T790M in exon 20
Which one of the following statements regarding acquired genetic alterations in patients with nonsmall-cell lung cancer (NSCLC) is NOT correct?
A.Mutations in EGFR and KRAS are mutually exclusive. B.Mutations in EGFR, BRAF and KRAS are mutually exclusive.
C.Mutations in KRAS and ALK are mutually exclusive. D.Mutations in BRAF, KRAS, and ALK are mutually exclusive.
E.Mutations in EGFR, BRAF, KRAS, and ALK are mutually exclusive.
F.None of the above.
F.None of the above.
EGFR, KRAS, BRAF, and ALK mutations are all mutually exclusive in patients with nonsmall-cell lung cancer (NSCLC).
Which one of the cancers causes the most deaths in the United States?
A.Breast cancer
B.Colorectal cancer
C.Lung cancer
D.Pancreatic cancer
E.Prostate cancer
C.Lung cancer
Which one of the following statements regarding erlotinib in therapy for nonsmall-cell lung cancer (NSCLC) is correct?
A.It targets the ligand-binding domain of the EGFR gene. B.It targets the tyrosine kinase domain of the EGFR gene. C.It targets the ligand-binding domain of the KRAS gene. D.It targets the tyrosine kinase domain of the KRAS gene. E.It targets the ligand-binding domain of the ALK gene. F.It targets the tyrosine kinase domain of the ALK gene.
B.It targets the tyrosine kinase domain of the EGFR gene
Which one of the following statements regarding erlotinib in therapy for nonsmall-cell lung cancer (NSCLC) is correct?
A.It is a monoclonal antibody that blocks the ligand-binding domain.
B.It is a small molecule that occupies the ATP-binding groove of the tyrosine kinase.
C.EGFR protein overexpression by immunohistochemistry can predict the response to erlotinib.
D.It can be used for patients with either EGFR or KRAS mutations, but not those with ALK mutations.
E.It can be used effectively to patients with EGFR mutations in exons 18 through 21.
B.It is a small molecule that occupies the ATP-binding groove of the tyrosine kinase.
How frequently do patients with lung adenocarcinoma have acquired KRAS mutations?
A.90%
B.75%
C.50%
D.20%
E.<5%
D.20%
How frequently do patients with nonsmall-cell lung cancer (NSCLC) have acquired an ALK rearrangement?
A.90%
B.75%
C.50%
D.20%
E.5%
E.5%
Which one of the following techniques is most commonly used to detect ALK genetic alterations in patients with nonsmall-cell lung cancer (NSCLC)?
A.FISH
B.OncoScan microarray
C.Quantitative PCR
D.Sanger sequencing
E.TaqMan genotyping assay
A.FISH
A patient with nonsmall-cell lung cancer (NSCLC) was found to have a deletion in exon 19 of EGFR. She relapsed on erlotinib after a partial remission that lasted 16 months. Which of the following exons of the EGFR gene would most likely be tested for resistance?
A.Exon 18
B.Exon 20
C.Exon 21
D.Exon 22
E.All of the above
B.Exon 20
the exon 20 T790M mutation is associated with acquired resistance to TKI therapy. c.2369C>T(p.Thr790Met)
erlotinib targets exon 19 deletions, exon 21 L858R, and exon 18 G719X.
Which one of the following results may be useful to predict whether a patient with nonsmall-cell lung cancer (NSCLC) may NOT response well to erlotinib?
A.Amplification of EGFR
B.p.G12A mutation in KRAS
C.p.L858R in exon 21 of EGFR
D.Polysomy of chromosome 7 including EGFR on 7p11.2 E.None of the above
B.p.G12A mutation in KRAS
Which one of the following results may be used to predict whether a patient with nonsmall-cell lung cancer (NSCLC) should NOT be treated with erlotinib?
A.Amplification of EGFR
B.Asian female nonsmoker
C.EML4-ALK translocation detected by FISH
D.p.L858R in exon 21 of EGFR
E.Polysomy of chromosome 7 including EGFR on 7p11.2
C.EML4-ALK translocation detected by FISH
EGFR mutations and ALK rearrangement in nonsmall-cell lung cancer (NSCLC) are mutually exclusive.
A fine-needle aspiration (FNA) of a nodule helped to establish the diagnosis of metastatic melanoma. Which one of the following molecular tests may be useful for prognosis and therapy?
A.ALK
B.BRAF
C.EGFR
D.KRAS
E.NRAS
B.BRAF
A BRAF assay with melting temperature analysis using dual hybridization fluorescence resonance energy transfer (FRET) probes was ordered to detect the V600E mutation. Both the sensor and anchor probes were 100% matched with the wild type BRAF sequence. Which one of the following statements regarding this FRET assay is correct?
A.The melting temperature is higher in the wild-type BRAF sequence than in the heterozygous mutant.
B.The melting temperature is higher in the heterozygous mutant than in the wild-type BRAF sequence.
C.The melting temperature is higher in the heterozygous mutant than in the homozygous BRAF mutant.
D.The melting temperature is higher in the homozygous mutant than in the wild-type BRAF sequence.
A.The melting temperature is higher in the wild-type BRAF sequence than in the heterozygous mutant.
Metastatic melanoma. A BRAF assay was ordered. Which one of the following results would be the most likely one for this patient?
A.BRAF K581S
B.BRAF V600D
C.BRAF V600E
D.BRAF V600K
E.BRAF K601E
F.Wild type
F.Wild type
So about 45% of patients have BRAF V600E, while 59% have wild type.
Metastatic melanoma. A BRAF assay was ordered. Which one of the following results would be the most likely one for this patient?
A.BRAF K581S
B.BRAF V600D
C.BRAF V600E
D.BRAF V600K
E.BRAF K601E
C.BRAF V600E
A BRAF assay with melting-temperature analysis using dual-hybridization fluorescence resonance energy transfer (FRET) probes was ordered to detect the V600E mutation. The melting temperature for the wild type was 64.5°C and for the V600E mutation 59.5°C. A melting temperature of 59.5°C was identified in the tumor sample from this patient. Which one of the following interpretations would be the most appropriate one?
A.A mutation in BRAF was identified in this specimen. B.A V600E mutation was identified in this specimen. C.Heterozygous V600E mutation was identified in this specimen.
D.Homozygous V600E mutation was identified in this specimen.
E.Sanger sequence is recommended to confirm the finding.
B.A V600E mutation was identified in this specimen.
A BRAF assay with melting-temperature analysis using dual-hybridization fluorescence resonance energy transfer (FRET) probes was ordered to detect the V600E mutation. The melting temperature for the wild type was 64.5°C and for the V600E mutation 59.5°C. A melting temperature of 54.5°C was identified besides the 64.5°C for the wild type. Which one of the following actions should be the most appropriate follow-up step?
A.Stating that the V600E mutation is identified and recommending BRAF inhibitor therapy.
B.Repeating the test to confirm the finding, then sequencing the region to confirm the mutation. C.Repeating the test to confirm the finding, then signing it out as a pathogenic variant of V600E.
D.Stating that a variant of V600E mutation is identified and recommending BRAF inhibitor therapy.
E.None of above.
B.Repeating the test to confirm the finding, then sequencing the region to confirm the mutation.
Acquired BRAF mutations are NOT common in:
A.Colorectal cancer
B.Ewing sarcoma
C.Metastatic melanoma
D.Nonsmall-cell lung cancer
E.Thyroid carcinoma
B.Ewing sarcoma
How frequently do patients with malignant melanomas have somatic mutations in BRAF?
A.90%
B.75%
C.45%
D.20%
E.<5%
C.45%
melanomas derived from skin without chronic sun-induced damage. In this category of melanoma, BRAF mutations are found in about 59% of samples.
Which one of the following statements regarding acquired BRAF mutations is NOT correct?
A.Mutations in BRAF are diagnostic for metastatic melanoma.
B.Mutations in BRAF are seen in benign melanocytic nevi.
C.Tests for BRAF mutations are important in predicting the response of the patient to BRAF inhibitors.
D.BRAF inhibitors prevent ligands from binding to the receptor.
E.Patients with V600K mutations respond well to BRAF inhibitors.
A.Mutations in BRAF are diagnostic for metastatic melanoma.
Real-time PCR with FRET probes and melting-curve analysis are most useful for detecting which one of the following?
A.Acquired CEBPA mutations for AML
B.BRAF mutations for melanoma
C.Duchenne muscular dystrophy
D.Fragile X
E.Hemophilia A
B.BRAF mutations for melanoma
intron 22 inversion in F8 for hemophilia A,
A BRAF V600E mutation can be used in all of the following clinical circumstances EXCEPT:
A.Diagnosing metastatic melanoma
B.Predicting a more aggressive thyroid cancer C.Predicting response to a BRAF inhibitor
D.Predicting response to anti-EGFR therapy in colorectal cancer
E.Ruling out Lynch syndrome in patients with colorectal cancer
A.Diagnosing metastatic melanoma
Which one of the following statements regarding erlotinib therapy for nonsmall-cell lung cancer (NSCLC) is correct?
A.It can be used for patients with mutations in ALK.
B.It can be used for patients with mutations in BRAF.
C.It can be used for patients with mutations in EGFR.
D.It can be used for patients with mutations in KRAS.
E.It can be used for patients with mutations in EGFR, BRAF, or KRAS.
F.It can be used for patients with mutations in EGFR, BRAF, KRAS, or ALK.
C.It can be used for patients with mutations in EGFR.
gefitinib (discontinued in the United States), erlotinib, and afatinib is limited to patients with activating EGFR mutations.
Vemurafenib and dabrafenib the BRAF V600E
In which type of thyroid cancers are the BRAF mutations most commonly seen?
A.Anaplastic thyroid cancer
B.Follicular thyroid cancer
C.Medullary thyroid cancer
D.Papillary thyroid cancer
E.Poorly differentiated thyroid cancer
D.Papillary thyroid cancer
How frequently do patients with papillary thyroid cancer have acquired mutations in BRAF?
A.90%
B.75%
C.45%
D.20%
E.<5%
C.45%
Which type of thyroid cancers do patients with type 2 multiple endocrine neoplasia (MEN2) most likely have?
A.Anaplastic thyroid cancer
B.Follicular thyroid cancer
C.Medullary thyroid cancer
D.Papillary thyroid cancer
E.Poorly differentiated thyroid cancer
C.Medullary thyroid cancer
Which type of thyroid cancers do patients with Cowden syndrome most likely have?
A.Anaplastic thyroid cancer
B.Follicular thyroid cancer
C.Medullary thyroid cancer
D.Papillary thyroid cancer
E.Poorly differentiated thyroid cancer
B.Follicular thyroid cancer
the risk of thyroid cancer in Cowden syndrome - PTEN is estimated to be between 3% and 38%
A biopsy of the lesion in his neck revealed a poorly differentiated carcinoma without features of papillary thyroid carcinoma. Which one of the following tests would be most useful in order to confirm or rule out metastatic papillary thyroid carcinoma?
A.BRAF V600E mutation
B.EGFR mutation analysis
C.EML4-ALK translocation
D.KRAS mutation analysis
E.NRAS mutation analysis
A.BRAF V600E mutation
Pt with remote prostate, thyroid and lung cancer. A PET scan demonstrated lesions in the hilum of the left lung. A biopsy of the lesion in his neck revealed a poorly differentiated carcinoma of unknown origin. Which one of the following tests would be most useful in order to confirm or rule out lung carcinoma?
A.BRAF V600E mutation
B.EGFR mutation analysis
C.EML4-ALK translocation FISH
D.KRAS mutation analysis
E.NRAS mutation analysis
E.NRAS mutation analysis
**shit question
Which one of the following genes is most likely mutated in follicular thyroid cancers as a somatic mutation?
A.ALK
B.BRAF
C.EGFR
D.KIT
E.RAS
F.RET
E.RAS
He contacted the pathologist to request a mutation analysis in order to guide treatment and delineate prognosis. Which one of the following genes most likely harbored an acquired pathogenic variant related to the response to imatinib if there was one in this patient?
A.BRAF
B.EGFR
C.KIT
D.PDGFRA
E.RAS
C.KIT
How frequently do patients with gastrointestinal stromal tumors (GISTs) have acquired mutations in KIT?
A.85%
B.65%
C.45%
D.25%
E.<5%
A.85%
How frequently do patients with gastrointestinal stromal tumors (GISTs) have acquired mutations in PDGFRA?
A.90%
B.70%
C.50%
D.20%
E.10%
E.10%
In which one of the following exons of KIT would the acquired pathogenic variant most likely be located in this patient?
A.Exon 9
B.Exon 11
C.Exon 13
D.Exon 14
E.Exon 17
B.Exon 11
70% juxtamembrane domain
exon 9 Extracellular dimerization motif 10-15%
exon 13 TK1D 1-3%
exon 17 TK2D activation loop 1-3%
secondary KIT mutations, particularly in the activation loop (D816V/Y - exon 17) and ATP-binding pocket (exons 13 and 14)
The results of the KIT assay turned to be negative. A reflex test was performed according to the note from the oncologist. Which one of the following genes would most likely be analyzed in the reflex test in order to further assess the prognosis, since the mutation analysis of KIT was negative?
A.ALK
B.BRAF
C.EGFR
D.PDGFRA
E.RAS
D.PDGFRA
KIT gene (85%), PDGFRA gene (5%–10%), or BRAF kinase rare - mutually exclusive
or NF1 (rare)
SDHA- Carney Stratakis syndrome - pulmonary chondroma, paraganglioma and GIST
A reflex molecular test for PDGFRA was performed according to the note from the oncologist, and the result was positive. Which one of the following exons of the PDGFRA gene most likely harbored the mutation?
A.Exon 12
B.Exon 13
C.Exon 14
D.Exon 15
E.Exon 16
F.Exon 17
G.Exon 18
G.Exon 18
In GIST PDGFRA mutations are found mostly in exons 18 (the tyrosine kinase 2 [TK2] domain, 5%), exon 12 (juxtamembrane domain; 1%) and 14 (tyrosine kinase 1 [TK1] domain; <1%).
Mutations except for D842V in exon 18 are sensitive to imatinib
The results of the KIT assay showed a p.Tyr570del in exon 11. Which one of the following statements is correct with regard to imatinib therapy?
A.The patient will respond well to imatinib.
B.The mutation in exon 11 of KIT is a positive predictive factor for overall survival.
C.The mutation in exon 11 of KIT is a positive predictive factor for progression-free survival.
D.Patients with mutations in exon 11 of KIT have a higher risk of secondary mutations.
E.Patients with mutations in exon 11 of KIT have improved tumor response with high-dose imatinib.
A.The patient will respond well to imatinib.
As compared to patients with KIT exon 9 mutations and wild-type GIST, patients with exon 11 mutations have a worse relapse-free survival and overall survival. However, their tumors have the highest sensitivity to imatinib, with a median duration of benefit of approximately 23 months. Patients with exon 11 mutations are less likely to respond to second-line sunitinib
The results of the KIT assay showed a p.Trp557_Lys558del in exon 11. After 6 months of imatinib therapy, the patient developed resistance. A molecular test was ordered for secondary mutations related to imatinib resistance. In which part of the KIT gene would mutations responsible for the imatinib resistance most likely be located in this patient?
A.Exon 9, 13, 14, or 17 of KIT
B.Exon 9 or 17 of KIT
C.Exon 12–16 of PDGFRA
D.Exon 13, 14, or 17 of KIT
E.Exon 17 or 18 of PDGFRA
*D.Exon 13, 14, or 17 of KIT
exons 13 and 14 - ATP binding pocket
exon 17 activation loop
KIT double mutants in exon 13/17 are resistant to both imatinib and sunitinib
The findings favored the diagnosis of epithelioid gastrointestinal stromal tumor (GIST) of low malignant potential. Which one of the following exons of KIT would most likely harbor the mutation in this patient if she has one predicted to respond to a high dose of imatinib therapy?
A.Exon 9
B.Exon 11
C.Exon 13
D.Exon 14
E.Exon 17
A.Exon 9
exon 11 mutations have the highest sensitivity to imatinib.
exon 9 mutations show intermediate sensitivity to imatinib. A high dose of imatinib is usually required.
The median duration of benefit from imatinib is approximately 7–12 months, as compared to 23 months for patients with exon 11 mutations.
As compared to patients with KIT exon 11 mutations, patients with exon 9 mutations have a better relapse-free survival and overall survival.
Patients with exon 9 mutations are more likely to respond to second-line sunitinib than patients with other KIT/PDGFRA mutations
A 41-year-old female was diagnosed with oligodendroglioma, WHO grade II. A partial resection of the left frontal lobe was done, which removed approximately 80% of the tumor. Which one of the following genetic tests would be appropriate for this patient?
A.ALK
B.BRAF
C.EGFR
D.RAS
E.1p/19q
E.1p/19q
A 41-year-old female was diagnosed with oligodendroglioma, WHO grade II. A partial resection of the left frontal lobe was done, which removed approximately 80% of the tumor. Which one of the following genetic abnormalities would this patient most likely have?
A.1p/19q amplification
B.1p/19q deletion
C.1p/19q duplication
D.Unclear
E.None of above
B.1p/19q deletion
How frequently does the 1p/19 codeletion appear in patients with oligodendroglioma?
A.100%
B.80%
C.60%
D.40%
E.20%
A.100%
*corrected answer given WHO CNS Tumors 5th ed 2021
A PCR-based loss-of-heterozygosity (LOH) analysis showed loss of 1p/19q in the oligodendroglioma. Which one of the following statements is NOT correct?
A.The 1p/19q codeletion is associated with a favorable response to chemotherapy.
B.The 1p/19q codeletion is associated with significantly better progression-free survival.
C.The 1p/19q codeletion is associated with significantly better overall survival.
D.Loss of 1p alone is associated with a favorable response to chemotherapy.
E.Loss of 19q alone is associated with a favorable response to chemotherapy.
E.Loss of 19q alone is associated with a favorable response to chemotherapy.
*can be seen in astrocytomas
The lab director decided to validate an assay for 1p/19q. With which one of the following brain tumors are losses of chromosomes 1p and 19q typically associated?
A.Ependymoma
B.Glioblastoma
C.Meningioma
D.Metastatic prostate cancer
E.Oligodendroglioma
E.Oligodendroglioma
A histological diagnosis of glioblastoma multiforme, WHO grade IV, was made. Which one of the following genetic tests would be most appropriate for diagnosis and estimation of prognosis and therapy in this patient?
A.BRAF
B.MGMT
C.PDGFRA
D.RAS
E.1p/19q FISH
B.MGMT
A histological diagnosis of glioblastoma multiforme, WHO grade IV, was made. Which one of the following genetic tests would be most appropriate for diagnosis and estimation of prognosis and therapy in this patient?
A.BRAF
B.EGFR
C.PDGFRA
D.RAS
E.1p/19q FISH
B.EGFR
A histological diagnosis of glioblastoma multiforme, WHO grade IV, was made. MGMT and EGFR genetic tests were ordered to confirm the diagnosis and estimate prognosis and therapy. Which one of the following MGMT regions would most likely be investigated in this patient?
A.Coding region
B.Exon
C.Intron
D.Promoter
E.UTRs
F.Whole gene
D.Promoter
Which one of the following techniques would most likely be used for the MGMT analysis?
A.Chromosome karyotype
B.Fluorescence in situ hybridization (FISH)
C.Methylation study
D.Sequencing
E.TaqMan SNP genotype
C.Methylation study
MGMT genetic tests were ordered, and turned out to be negative. The oncologist ordered another genetic test in order to further confirm the diagnosis and estimate prognosis and therapy. Which one of the following genes would most likely be tested when the MGMT genetic test was negative in this patient?
A.BRAF
B.EGFR
C.PDGFRA
D.RAS
E.None of the above
B.EGFR
MGMT and EGFR genetic tests were ordered to confirm the diagnosis and estimate prognosis and therapy. Which one of the following genetic alterations would the EGFR assay most likely be designed to detect in this patient?
A.Amplifications
B.Deletions
C.Duplications
D.Microsatellite instability
E.Single-nucleotide mutations
F.Translocation
A.Amplifications
Gain of 7
EGFRvIII exons 2-7
MGMT and EGFR genetic tests were ordered to confirm the diagnosis of glioblastoma and estimate prognosis and therapy. Which one of the following techniques would most likely be used for the EGFR analysis in order to assist decision making about therapy?
A.Chromosome karyotype
B.Fluorescence in situ hybridization (FISH)
C.Methylation study
D.Sequencing
E.TaqMan SNP genotype
B.Fluorescence in situ hybridization (FISH)
MGMT genetic tests were ordered for a glioblastoma, and the results were positive for methylation in the promoter region. Which one of the following statements would be the most appropriate interpretation of these results?
A.The patient would be resistant to the alkylating therapy.
B.The patient would respond well to the alkylating therapy.
C.The sample from this patient was bisulfite conversion–positive.
D.The overall survival of this patient would be poor. E.None of the above.
B.The patient would respond well to the alkylating therapy.
frequency of MGMT promoter methylation was 45%. Irrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor. Among patients whose tumor contained a methylated MGMT promoter, a survival benefit was observed in patients treated with temozolomide and radiotherapy. The median survival was 22 months for patients with both temozolomide and radiotherapy, as compared with 15 months among those who were assigned to only radiotherapy
MGMT and EGFR genetic tests were ordered for a glioblastoma, and results were positive for EGFR amplification. Which one of the following statements would be an appropriate interpretation of these results?
A.The patient would respond well to chemotherapy. B.The patient would respond well to radiation therapy. C.The patient would respond well to combined chemotherapy and radiation therapy.
D.The patient had oligodendroglioma instead of glioblastoma.
E.The overall survival of this patient would be poor.
E.The overall survival of this patient would be poor.
EGFR gene amplification has been related to decrease overall survival and resistance of glioblastoma multiforme (GBM) cells toward radiation and chemotherapy.
Which one of the following represents the DNA modification caused by sodium bisulfite treatment for methylation study in the MGMT genetic analysis?
A.A>G
B.C>T
C.C>U
D.T>U
E.None of above
C.C>U
MGMT genetic tests were ordered, and results showed partial MGMT methylation. Which one of the following might result in a pattern of partial methylation in the glioblastoma specimen from this patient?
A.Incomplete conversion
B.Presence of nonneoplastic cells
C.Tumor heterogeneity
D.All of the above
E.None of the above
D.All of the above
Which one of the following abnormalities is most likely seen in patients with neuroblastoma?
A.Amplification of ALK
B.c.3520T>A (p.F1174I) in ALK
C.Deletion of the ALK gene
D.inv(2)(p21p23) involving ALK
E.t(2;5)(p23;q35) involving ALK
B.c.3520T>A (p.F1174I) in ALK
Which one of the following abnormalities is most likely seen in patients with anaplastic large-cell lymphoma?
A.Amplification of ALK
B.c.3520T>A (p.F1174I) in ALK
C.Deletion of the ALK gene
D.inv(2)(p21p23) involving ALK
E.t(2;5)(p23;q35) involving ALK
E.t(2;5)(p23;q35) involving ALK
80% NPM1-ALK fusion
ALK-positive ALCL has a better prognosis than ALK-negative ALCL, and it is diagnosed more frequently in younger patients
With which one of the following malignancies is a MYCN amplification most likely associated?
A.Acute myeloid leukemia
B.Astrocytoma
C.B precursor lymphoid neoplasm
D.Neuroblastoma
E.Rhabdomyosarcoma
D.Neuroblastoma
Diagnosis of metastatic neuroblastoma, poorly differentiated. A genetic test was ordered to assess the prognosis. Which one of the following acquired genetic changes would most likely be detected in this patient?
A.C-MYC amplification
B.C-MYC translocation
C.N-MYC amplification
D.N-MYC translocation
E.All of the above F.None of the above
C.N-MYC amplification
Which one of the following acquired abnormalities is most likely seen in patients with nonsmall-cell lung cancer (NSCLC)?
A.Amplification of ALK
B.c.3520T>A (p.F1174I) in ALK
C.Deletion of the ALK gene
D.inv(2)(p21p23) involving ALK
E.t(2;5)(p23;q35) involving ALK
D.inv(2)(p21p23) involving ALK
ALK-EML4
Approximately 3%–7% of lung tumors harbor ALK fusions.
64 yo smoker. Which one of the following exons of the EGFR gene would most likely be investigated in this molecular battery test for NSCLC?
A.Exon 9
B.Exon 11
C.Exon 13
D.Exon 14
E.Exon 19
E.Exon 19
Acquired EGFR mutations are present in 10%–15% of patients with nonsmall-cell lung carcinoma (NSCLC) in the United States. Tumors with EGFR mutations occur at a higher frequency in East Asians than in non-Asians (30% vs. 8%), in women than in men (59% vs. 26%), in never-smokers than in ever-smokers (66% vs. 22%), and in adenocarcinomas (ADCs) than in other NSCLC histologies (49% vs. 2%). The two most common EGFR mutations are located in exon 19 and exon 21. Gefitinib and erlotinib are the first generation of EGFR tyrosine kinase inhibitors (TKIs),
64 yo smoker. Which one of the following exons of the EGFR gene would most likely be investigated in this molecular battery test for NSCLC?
A.Exon 9
B.Exon 10
C.Exon 20
D.Exon 21
E.All of the above
F.None of the above
D.Exon 21
most common EGFR mutations are located in exon 19 and exon 21.
A molecular battery test was ordered, and an acquired pathogenic variant in exon 19 of the EGFR gene was detected in the tumor specimen. Which one of the following genetic changes in the EGFR gene would this patient most likely have?
A.Amplification
B.In-frame in/dels
C.Out-of-frame in/dels
D.Point mutation
E.All of the above
F.None of the above
B.In-frame in/dels
The two most common EGFR mutations are located in exon 19 and exon 21. The one in exon 19 is a short in-frame deletion.
A molecular battery test was ordered, and an acquired pathogenic variant in exon 21 of the EGFR gene was detected in the tumor specimen. Which one of the following genetic changes in the EGFR gene would this patient most likely have?
A.Amplification
B.In-frame in/dels
C.Out-of-frame in/dels
D.Point mutation
E.All of the above
F.None of the above
D.Point mutation
The one in exon 21 is a point mutation (CTG to CGG) at nucleotide 2573 that results in substitution of leucine by arginine at codon 858 (L858R).
A molecular battery test was ordered, and an acquired pathogenic variant in exon 21 of the EGFR gene was detected in the tumor specimen. Which kind of clinical significances would this variant in the EGFR gene have for this patient?
A.Diagnostic
B.Prognostic
C.Treatment decisions
D.All of the above
C.Treatment decisions
A molecular battery test was ordered, and an acquired pathogenic variant in exon 21 of the EGFR gene was detected. Gefitinib, a first-generation EGFR tyrosine kinase inhibitor (TKI), was used for treatment. After 6 months, the patient stopped responding to the therapy. The oncologist ordered a molecular test to confirm the resistance. Which one of the following exons of the EGFR gene would most likely be investigated for the resistance?
A.Exon 18
B.Exon 19
C.Exon 20
D.Exon 21
E.All of the above
F.None of the above
C.Exon 20
c.2396C>T(p.T790M) mutation in the exon 20 of the EGFR gene is associated with acquired resistance to erlotinib/gefitinib (EGFR TKI)
A molecular battery test was ordered, and an acquired pathogenic variant in exon 21 of the EGFR gene was detected. Gefitinib, a first-generation EGFR tyrosine kinase inhibitor (TKI), was used for treatment. After 6 months, the patient stopped responding to the therapy. The oncologist ordered an EGFR test to confirm the resistance, which turned out to be negative. Which one of the following genetic alterations would most likely be investigated further for the resistance?
A.Amplification of ALK
B.Amplification of HER2
C.Amplification of c-MET
D.Amplification of MYCN
E.Amplification of RUNX1
F.None of the above
C.Amplification of c-MET
c-MET gene encodes a receptor tyrosine kinase—hepatocyte growth factor receptor (HGFR).
A transcutaneous needle biopsy and pathological examinations confirmed the diagnosis of nonsmall-cell lung carcinoma (NSCLC), adenocarcinoma (ADC) subtype. A molecular battery test was ordered. Which one of the following genetic alterations in the ALK gene would most likely be investigated for therapy?
A.Amplification
B.Deletion
C.Duplication
D.Inversion
E.Point mutation
F.All of the above
G.None of the above
D.Inversion
The EML4 gene is located on 2p21, and the ALK gene is located on 2p23.
Which one of the following techniques would most likely be used for the ALK analysis in a NSCLC case?
Which one of the following techniques would most likely be used for the ALK analysis in this case?
A.Chromosome karyotype
B.Fluorescence in situ hybridization (FISH)
C.Methylation study
D.Sequencing
E.TaqMan SNP genotype
B.Fluorescence in situ hybridization (FISH)
A transcutaneous needle biopsy and pathological examinations confirmed the diagnosis of nonsmall-cell lung carcinoma (NSCLC), adenocarcinoma (ADC) subtype. A molecular battery test was ordered. Which one of the following exons of the KRAS gene would most likely be investigated in this molecular battery test?
A.Exon 2
B.Exon 5
C.Exon 19
D.Exon 21
E.All of the above
F.None of the above
A.Exon 2
An acquired pathogenic variant in the KRAS gene was detected in a NSCLC. Which one of the following genetic changes in the KRAS gene would this patient most likely have?
A.Amplification
B.In-frame in/dels
C.Out-of-frame in/dels
D.Point mutation
E.All of the above
F.None of the above
D.Point mutation
A molecular battery test was ordered, which included a sequencing assay for exon 2 of the KRAS gene. In addition to exon 2, which one of the following exons of the KRAS gene might also harbor acquired pathogenic variants for NSCLC?
A.Exon 3
B.Exon 5
C.Exon 19
D.Exon 21
E.All of the above
F.None of the above
A.Exon 3
A molecular battery test was ordered, which included a sequencing assay for exon 2 of the KRAS gene. Which kind of clinical significance would a variant in the KRAS gene have for this NSLC patient?
A.Diagnostic
B.Prognostic
C.Treatment decisions
D.All of the above
E.None of the above
C.Treatment decisions
A molecular battery test was ordered, and BRAF V600E was detected. Which kind of clinical significance would this variant in the BRAF gene have in this NSCLC patient?
A.Diagnostic
B.Prognostic
C.Treatment decisions
D.All of the above
E.None of the above
C.Treatment decisions
A transcutaneous needle biopsy and pathological examinations confirmed the diagnosis of nonsmall-cell lung carcinoma (NSCLC), adenocarcinoma (ADC) subtype. A molecular battery test was ordered. Which one of the following genetic assays would most likely NOT be included in this battery test?
A.ALK mutations in the kinase domain
B.BRAF mutations
C.EGFR in frame deletions of exon 19
D.EGFR L858R mutation in exon 21
E.KRAS mutations at codon 12 and 13
F.None of the above
A.ALK mutations in the kinase domain
Which one of the following genes in this panel is associated with high microsatellite instability (MSI)?
A.BRAF
B.KRAS
C.NRAS
D.SMAD4
E.None of the above
A.BRAF
A next-generation sequencing panel (NGS) for solid tumor was ordered, and an acquired pathogenic variant in the KRAS gene was identified in the COAD. Which one of the following prognoses would this patient most likely have?
A.Favorable risk
B.Intermediate risk
C.Unfavorable risk
D.Unclear
E.None of the above
C.Unfavorable risk
10-15% CRC
A next-generation sequencing (NGS) panel for solid tumor was ordered, and BRAF V600E mutation was identified. Which one of the following prognoses would this patient with CRC most likely have?
A.Favorable risk
B.Intermediate risk
C.Unfavorable risk
D.Unclear
E.None of the above
C.Unfavorable risk
30-40% CRC
A molecular test of the tumor sample revealed high microsatellite instabilities and MLH1 hypermethylation. Which one of the following genes would most likely harbor an acquired pathogenic variant with therapeutic significances?
A.ALK
B.BRAF
C.EGFR
D.KRAS
E.NRAS
F.None of above
B.BRAF
A molecular test of the ascending colon tumor sample revealed an acquired pathogenic variant in the KRAS gene, c.182A>G(p.Q61R). Which one of the following interpretations would most likely be appropriate for this patient?
A.The patient would respond well to BRAF inhibitor therapy.
B.The patient would respond well to EGFR inhibitor therapy.
C.The patient would respond well to KRAS inhibitor therapy.
D.All of the above.
E.None of the above.
E.None of the above.
55 yo Caucasian woman with ascending colon tumor. Histopathological examinations demonstrated adenomatous colorectal carcinoma (CRC). A molecular test of the tumor sample for acquired pathogenic variants in the KRAS was ordered, and the results were negative. Which one of the following therapies would most likely be appropriate for this patient?
A.BRAF inhibitor
B.EGFR inhibitor
C.KRAS inhibitor
D.All of the above
E.None of the above
B.EGFR inhibitor
Which one of the following is a limitation of NGS for DNA analyses of solid tumors?
A.It needs at least a few micrograms of DNA.
B.It is not a sensitive test for detecting low-level mosaicism.
C.It cannot be used on formalin-fixed, paraffin-embedded (FFPE) samples.
D.It cannot detect inv(2) for ALK rearrangement.
E.All of the above.
F.None of the above.
D.It cannot detect inv(2) for ALK rearrangement.
48 yo man with left proximal arm melanoma. Which one of the following BRAF V600 mutations would the patient most likely have?
A.V600D
B.V600E
C.V600G
D.V600K
E.V600R
F.None of the above
B.V600E
Which one of the following BRAF V600 mutations would make the patient suitable for treatment with trametinib (Mekinist tablets, GlaxoSmithKline, LLC) and dabrafenib (Tafinlar capsules, GlaxoSmithKline, LLC) treatment besides V600E, according to the FDA-approval?
A.V600D
B.V600G
C.V600K
D.V600R
E.None of the above
C.V600K
Histological examinations of a punch biopsy led to a diagnosis of Langerhans-cell histiocytosis (LCH). Which one of the following genes would most likely be somatically mutated in this patient?
A.ALK
B.BRAF
C.EGFR
D.KRAS
E.NRAS
F.None of the above
B.BRAF
Which one of the following disorders MOST LIKELY harbors the BRAF V600E mutation?
A.Colorectal carcinoma
B.Langerhans-cell histiocytosis
C.Metastatic melanoma
D.Nonsmall-cell lung cancer
E.Papillary thyroid carcinoma
F.Renal-cell carcinoma
G.None of the above
C.Metastatic melanoma
80% in melanomas and nevi, to 1%–3% in lung cancers and 5% in colorectal cancer.
Which one of the following disorders LEAST likely harbors the BRAF V600E mutation?
A.Colorectal carcinoma
B.Langerhans-cell histiocytosis
C.Metastatic melanoma
D.Nonsmall-cell lung cancer
E.Papillary thyroid carcinoma
F.Renal-cell carcinoma (RCC)
G.None of the above
F.Renal-cell carcinoma (RCC)
A scientist in a clinical molecular laboratory decides to validate a targeted solid tumor next-generation sequencing (NGS) panel including BRAF, EGFR, KRAS, NRAS, and 13 other genes. For which one of the following malignancies is this assay NOT appropriate?
A.Alveolar rhabdomyosarcoma
B.Colorectal carcinoma
C.Embryonal rhabdomyosarcoma
D.Metastatic melanoma
E.Nonsmall-cell lung cancer
F.Papillary thyroid carcinoma
G.None of the above
A.Alveolar rhabdomyosarcoma
Alveolar rhabdomyosarcoma - PAX7-FOXO1 or a PAX3-FOXO1
Aberrant genes observed in embryonal rhabdomyosarcoma include BRAF, CTNNB1, FGFR4, HRAS, KRAS, NRAS, PIK3CA, and PTPN11
