Oncology consititutional Flashcards
What is the detection sensitivity of the revised Amsterdam criteria (Amsterdam II criteria) to the clinical diagnosis of Lynch syndrome?
A. 60%
B. 70%
C. 80%
D. 90%
E. 100%
F.None of the above
C. 80%
At least 3 relatives with Lynch syndrome-associated cancer: This includes colorectal, endometrial, small bowel, ureter, or renal pelvis cancer.
At least 2 successive generations affected:
One first-degree relative of the other two
At least 1 relative diagnosed before age 50
Rule out FAP
Prenatal care at 6 wks and maternal brother with FAP. The couple wanted to find out the risk of their first unborn child developing FAP. What should be the next step in the workup be to estimate the risk in this family?
A.Testing the wife for the APC gene
B.Recommending CVS to test the fetus for the APC gene
C.Testing the wife’s brother for the APC gene
D.Recommending that the couple test the child after he/she is born E.Recommending amniocentesis to test the fetus for the APC gene
C.Testing the wife’s brother for the APC gene
Prenatal care at 6 wks and maternal brother with FAP. The couple wanted to find out the risk of their first unborn child developing FAP. Which one of the following assays would most likely be used for the genetic test to establish/rule out genetic etiologies in this family?
A. Chromosome microarray B.Denaturing high-performance liquid chromatography (dHPLC) analysis of the APC gene
C. Exome sequencing
D.Multiplex ligation-dependent probe amplification (MLPA) analysis of the APC gene
E.Next-generation sequencing for hereditary colorectal cancers F.Sequence analysis of the APC gene
F.Sequence analysis of the APC gene
A 48-year-old male was diagnosed with colon cancer. The family history was uneventful. Which one of the following hereditary cancer syndromes should be ruled out in this patient even with the negative family history?
A.Familial adenomatous polyposis (FAP) B. Juvenile polyposis syndrome
C. Lynch syndrome
D. MYH-associated polyposis
E. Peutz–Jeghers syndrome
C. Lynch syndrome
ALL new CRC
MLH1 molecular test for female patient, and the results were positive. Which one of the following cancers would this female patient NOT have an increased risk of developing?
A. Endometrial cancer
B. Hepatobiliary tract cancer
C. Lung cancer
D. Ovarian cancer
E. Stomach cancer
C. Lung cancer
NOT lung or breast cancer
MLH1 molecular test for female patient, and the results were positive. Which one of the following cancers would this female patient NOT have an increased risk of developing?
A. Breast cancer
B. Endometrial cancer
C. Hepatobiliary tract cancer
D. Ovarian cancer
E. Stomach cancer
A. Breast cancer
NOT lung or breast cancer
Colorectal cancer (CRC). Microsatellite instability (MSI) analyses of the tumor sample showed a high level of MSI. What would be the most likely diagnosis for this patient?
A.Familial adenomatous polyposis (FAP) B. Lynch syndrome
C. MYH-associated polyposis
D. Sporadic colon cancer
E.None of the above
D. Sporadic colon cancer
Approximately 10%–15% of sporadic CRCs also exhibit MSI. The molecular basis for instability in these tumors is most often methylation of the MLH1
Colorectal cancer (CRC). Microsatellite instability (MSI) analyses of the tumor sample demonstrated MSI in 40% of markers. What would be the most likely diagnosis for this patient?
A.Familial adenomatous polyposis (FAP) B. Lynch syndrome
C. MYH-associated polyposis
D. Sporadic colon cancer
E.None of the above
D. Sporadic colon cancer
CRC in older male. Which one of the following specimens would be most appropriate for the MSI test in this patient?
A. Buccal swab
B. Peripheral-blood sample
C. Resected tumor tissue
D. Skin tissue
E. Urine sample
F.None of the above
C. Resected tumor tissue
CRC in older male. Which one of the following microsatellites would most likely demonstrate instability if the patient had Lynch syndrome?
A. A mononucleotide polymorphism
B. A trinucleotide polymorphism
C. A pentanucleotide polymorphism
D. A single-nucleotide polymorphism
E. Unclear
A. A mononucleotide polymorphism
Mononucleotide repeat markers are more likely to be unstable than other microsatellites in mismatch repair (MMR)–deficient tumors. - more likely to be homozygous mono repeats
The MSI Analysis System, Version 1.2, from Promega is a fluorescent multiplex PCR–based method that detects microsatellite instability (MSI) with five mononucleotide repeats, and two pentanucleotide repeats are the identity controls.
The ABI kit is a fluorescent multiplex PCR–based method that detects microsatellite instability (MSI) with five dinucleotide repeats.
CRC older male. Microsatellite instability (MSI) analyses of the tumor sample showed a high level of MSI. What percentage (or more) of the repeats would be unstable if an MSI-high profile was reported?
A. 20%
B. 40%
C. 60%
D. 80%
E. 100%
B. 40%
An MSI-low profile is reported if fewer than 40% of repeats are unstable.
Which one of the following type of malignancies, besides colon cancer, has a high incidence of microsatellite instability (MSI)?
A. Cervical cancer
B. Endometrial carcinoma
C. Intestinal cancer
D. Ovarian cancer
E. Stomach cancer
B. Endometrial carcinoma
How frequently is MSI seen in patients with endometrial carcinoma?
A. <1% B.
5%–10%
C. 20%–30%
D. 40%–50%
E. >90%
C. 20%–30%
How frequently is microsatellite instability (MSI) seen in Lynch syndrome patients with colorectal carcinoma (CRC) ?
A. <1%
B. 5%–10%
C. 20%–30%
D. 40%–50%
E. >99%
E. >99%
autosomal dominant disease with a population incidence of 1 in 400–500 and is responsible for about 3% of all CRCs.
The oncologist contacted the pathologist to request microsatellite instability (MSI) analysis to rule out Lynch syndrome. The results showed three of five mononucleotide polymorphisms were unstable. However, it also showed that one of the control pentanucleotide polymorphisms had allele 20/20 in the tumor tissue, while it had alleles 20/24 in the peripheral-blood sample from the patient. Which one of the following statements would be the most appropriate reaction to this result? A.The molecular MSI test did not work; immunohistochemistry staining for MSI is recommended.
B.Repeat the test with the same specimens.
C.Report out as MSI-high profile in the tumor sample with loss of heterozygosity (LOH).
D.Second tumor and peripheral-blood specimens from the same patient should be requested in order to run the test again.
E.The personal identification test should be run on both the tumor and peripheral-blood specimens to confirm that they are from same patient.
C.Report out as MSI-high profile in the tumor sample with loss of heterozygosity (LOH).
48 yo woman with CRC and a brother diagnosed with colon cancer at age 45 and her mother diagnosed with endometrial cancer at age 50. She also had one unaffected sister. The physical examination was unremarkable. Of which one of the following hereditary cancer syndromes should we be suspicious in this family?
A. Cowden syndrome
B. Li–Fraumeni syndrome
C. Lynch syndrome
D.Multiple endocrine neoplasia type 1 (MEN1)
E. von Hippel–Lindau disease
C. Lynch syndrome
Which one of the following genetic tests should be done first to rule out genetic etiologies, according to ACMG Technical Standard and Guidelines for Genetic Testings for Inherited CRC, 2014?
A. APC, MUTYH
B.BRAF gene p.V600E mutation
C. Exome sequencing
D. MSI
E.NGS with BMPR1A, SMAD2, STK11, and PTEN
F.NGS with MLH1, MSH2, MSH6, PMS2, and PSM6
D. MSI
Microsatellite instability (MSI) testing revealed a high level of MSI. Which one of the following genetic tests should be done next to further rule out genetic etiologies, according to the ACMG Technical Standard and Guidelines for Genetic Testings for Inherited CRC, 2014?A. APC, MUTYH
B.BRAF gene p.V600E mutation
C. Exome sequencing
D. Microsatellite instability test
E.NGS with BMPR1A, SMAD2, STK11, and PTEN
F.NGS with MLH1, MSH2, MSH6, PMS2, and PSM6
B.BRAF gene p.V600E mutation
BMPR1A and SMAD4 genes are associated with autosomal dominant juvenile polyposis syndrome. Germline pathogenic variants in the STK11 gene are associated with autosomal dominant Peutz–Jeghers syndrome. Germline pathogenic variants in the PTEN gene are associated with autosomal dominant PTEN hamartomatous tumor syndrome.
48 yo woman with CRC and a brother diagnosed with colon cancer at age 45 and her mother diagnosed with endometrial cancer at age 50. She also had one unaffected sister.Which one of following assays would be appropriate for this family in order to rule out genetic etiologies?
A. Chromosome microarray
B.Multiplex ligation-dependent probe amplification (MLPA)
C.NGS with BMPR1A, SMAD2, STK11, and PTEN
D.NGS with MLH1, MSH2, MSH6 and PMS2
E.No need for genetic tests
D.NGS with MLH1, MSH2, MSH6 and PMS2
*edited to remove PSM6 typo
The results demonstrated that the patient had a deleterious pathogenic variant in the PMS2 gene. Which one of following hereditary cancer syndromes did the patient have?
A. Familial adenomatous polyposis
B. Juvenile polyposis syndrome
C. Lynch syndrome
D. MYH-associated polyposis
E. Peutz–Jeghers syndrome
C. Lynch syndrome
Lynch syndrome most common inherited CRC. 1in 500 and 3% of CRCs. Patients with Lynch syndrome have up to an 80% lifetime risk of developing colon cancer. Women with Lynch syndrome have up to a 60% lifetime risk of developing endometrial carcinoma. Affected individuals are also at greater risk for other cancers, such as stomach, ovarian, small bowel, biliary, renal pelvis, and ureteral cancers.
Most individuals with LS have a germline pathogenic variant in one of the DNA mismatch repair genes. Which one of following genes is NOT a mismatch repair gene?
A. APC
B. MLH1
C. MLH3
D. MSH6
E. PMS1
A. APC
Which one of following genes is associated with Lynch syndrome, but is NOT a mismatch repair gene?
A. EpCAM
B. MLH1
C. MLH3
D. MSH6
E. PMS1
F. PMS2
A. EpCAM
The results demonstrated the patient had a deletion in the EpCAM gene. Which one of following microsatellite instability (MSI) findings would this patient most likely have?
A. MSI-high
B. MSI-low
C. MSI-stable
D. Not sure
E. None of the above
A. MSI-high
The results demonstrated the patient had a deletion in the EpCAM gene. Which one of following immunohistochemistry (IHC) findings would this patient have? A.Loss expression of MLH1 and MSH2 B.Loss expression of MLH1 and PMS2 C.Loss expression of MSH2 and MSH6 D.Loss expression of MSH2 and PMS2 E.None of the above
C.Loss expression of MSH2 and MSH6
Paternal CRC and paternal aunt UEC. The physical examination was unremarkable. Which one of the following genes would most likely NOT provide information to confirm or rule out genetic etiologies in this patient?
A. MLH1
B. MSH2
C. MSH3
D. MSH6
E. PMS2
C. MSH3
The results showed no staining for MHL1 and PMS2, but staining for MSH2 and MSH6. A BRAF mutation test was positive for the V600E mutation. Which one of the following mutations is most likely detectable in tumor?
A. p.Arg134Ter in PMS2
B.Promoter hypermethylation in PMS2 C. p.Pro622Leu in MSH2
D.Promoter hypermethylation in MSH2 E. p.Ser252Ter in MHL1
F.Promoter hypermethylation in MHL1
F.Promoter hypermethylation in MHL1
Lynch syndrome is the most common cause of inherited colorectal cancer (CRC), characterized by a significantly increased risk for CRC and endometrial cancer as well as a risk of several other malignancies. Which one of the following DNA mismatch repair genes tends to be hypermethylated in individuals with sporadic CRCs?
A. MLH1
B. MLH3
C. MSH6
D. PMS1
E. PMS2
A. MLH1
Approximately 10%–15% of sporadic CRCs also exhibit MSI. The molecular basis for instability in these sporadic tumors is most often methylation of the MLH1 promoter, leading to loss of both mRNA and protein expression
A molecular test confirmed that the patient had a pathogenic variant in the MSH2 gene. Which one of the following malignancies would this patient have the highest risk of developing in her lifetime? A. Cervical cancer
B. Endometrial carcinoma
C. Hepatocellular carcinoma
D. Ovarian cancer
E. Stomach cancer
B. Endometrial carcinoma
40-60% risk for both CRC and UEC
A molecular test confirmed the patient had a pathogenic variant in the MSH2 gene. What would be this patient’s risk of developing colorectal cancer in her lifetime?
A. 20%
B. 40%
C. 60%
D. 80%
E. >99%
D. 80%
Patients with Lynch syndrome have up to an 80% lifetime risk of developing colon cancer and, in women, up to a 60% lifetime risk of developing endometrial carcinoma.
A molecular test confirmed the patient had a pathogenic variant in the MSH2 gene. What would be this patient’s risk of developing endometrial carcinoma in her lifetime?
A. 20%
B. 40%
C. 60%
D. 80%
E. >99%
C. 60%
Patients with Lynch syndrome have up to an 80% lifetime risk of developing colon cancer and, in women, up to a 60% lifetime risk of developing endometrial carcinoma.
The results showed no staining for MHL1 and PMS2, but staining for MSH2 and MSH6. Which one of the following would be appropriate next step in the workup for this patient?
A. BRAF mutation analysis
B.Diagnosing the patient with endometrial adenocarcinoma without genetic etiology
C.Diagnosing the patient with Lynch syndrome
D.Performing next-generation sequencing for all the genes for hereditary colon cancer
E.Performing sequencing analysis of MLH1 and PMS1
F.Performing sequencing analysis of MSH2 and MSH6
E.Performing sequencing analysis of MLH1 and PMS1
The results showed MSI in three of six markers, loss of expression of MSH2, and normal expression of MLH1. Molecular genetic tests of both MSH2 and MSH6 were negative. Which one of the following tests might be the next step in the workup to further rule out Lynch syndrome in this patient?
A.A larger next-generation sequencing panel for hereditary colon cancer syndromes
B.BRAF gene p.V600E mutation test C.EpCAM gene 3′ deletion test
D.MLH1 promoter methylation study E.MLH1 and PMS2 gene-mutation test
C.EpCAM gene 3′ deletion test
The results showed MSI in three of six markers, loss of expression of MSH2, and normal expression of MLH1. Molecular genetic tests of both MSH2 and MSH6 were negative. To further rule out Lynch syndrome in this patient, the medical geneticist ordered a molecular test on the EpCAM gene, and the results turned out to be positive. Which one of the following changes in EpCAM would most likely be detected in this patient?
A. Deletion
B. Frameshift mutation
C. Insertion
D. Missense mutation
E. Nonsense mutation
A. Deletion
The results showed MSI in three of six markers, loss of expression of MSH2, and normal expression of MLH1. Molecular genetic tests of both MSH2 and MSH6 were negative. To further rule out Lynch syndrome in this patient, the medical geneticist ordered a molecular test on the EpCAM gene, and a deletion on the 3′ end of the gene was detected. How would the deletion in EpCAM cause Lynch syndrome in this patient?
A.It causes somatic hypermethylation of MLH1.
B.It causes somatic hypermethylation of MSH2.
C.It causes somatic hypermethylation of MSH6.
D.It causes somatic hypermethylation of PMS2.
E.None of the above.
B.It causes somatic hypermethylation of MSH2.
The results of a CRC showed a high level of MSI, loss of expression of MLH1, and normal expression of MSH2. Predictably, which one of the following genes lose expression, too, in the tumor tissue from this patient?
A. BRAF
B. MSH6
C. PMS2
D.All of the above
E.None of the above
C. PMS2
The results showed high level of MSI, loss of expression of MSH2, and normal expression of MLH1. Predictably which one of the following genes would lose expression, too, in the tumor tissue from this patient?
A. BRAF
B. MSH6
C. PMS2
D.All of the above
E.None of the above
B. MSH6
The results showed 50% of MSI, loss of expression of MLH1, and normal expression of MSH2. What would be the next step in the workup according to ACMG Technical Standard and Guidelines for Genetic Testing for Inherited CRC, 2014?
A. BRAF p.V600E test
B. BRAF p.V600K test
C. BRAF sequence
D.MLH1 and MSH2 sequence
E.MLH1 and MSH6 sequence
F.MLH1 and PMS2 sequence
A. BRAF p.V600E test
The results showed MSI in three of six markers and loss of expression of MSH2 and MSH6. What would be the next step in the workup according to ACMG Technical Standard and Guidelines for Genetic Testing for Inherited CRC, 2014?A.BRAF p.V600E mutation test
B. BRAF p.V600K test
C. BRAF sequence
D. MSH2 sequence
E. MSH6 gene-mutation test
F.MSH2 and MSH6 gene-mutation test
F.MSH2 and MSH6 gene-mutation test
48 yo man with adenomatous polyps throughout the colon. His family history was negative for polyposis and/or CRC. What would be the most appropriate molecular test as the next step in the workup to rule out genetic etiologies in this patient?
A.Sequence the APC gene with reflex to APC del/dup analysis
B.Sequence the MUTYH gene with reflex to MUTYH del/dup analysis
C.Sequence the MLH1 gene with reflex to MLH1 del/dup analysis
D.Sequence the MSH2 gene with reflex to MSH2 del/dup analysis
E.Sequence the APC and MUTYH genes with reflex to APC and MUTYH del/dup analysis
F.Sequence the MLH1 and MSH2 genes with reflex to MLH1 and MSH2 del/dup analysis
E.Sequence the APC and MUTYH genes with reflex to APC and MUTYH del/dup analysis
absence of family history in MAP and the high rate of de novo mutations in attenuated FAP and FAP (20%), analysis of both MUTYH and APC gene mutations should be considered for patients with or without adenomatous polyps.
All of the following tumors are consistent with Lynch syndrome, EXCEPT:
A.BRAF mutation–negative, MLH1 methylation negative, MSI-high colorectal cancer
B.MLH1 immunohistochemistry (IHC)–negative, BRAF mutation–positive colorectal cancer
C.MSH2 and MSH6 immunohistochemistry (IHC)–negative endometrial adenocarcinoma
D.MSI-high, MLH1 methylation–negative endometrial adenocarcinoma
E.MSI-high, MLH1 immunohistochemistry (IHC)–negative endometrial adenocarcinoma
B.MLH1 immunohistochemistry (IHC)–negative, BRAF mutation–positive colorectal cancer
Adenomatous polyps throughout the colon. The family history was negative for polyposis and/or CRC. A KRAS mutation analysis showed that the patient had a somatic c.34G>T mutation. Which one of the hereditary cancer predisposition syndromes would this patient most likely have if she had one? A. Familial adenomatous polyposis
B. Lynch syndrome
C. MYH-associated polyposis
D. Peutz–Jeghers syndrome
E. PTEN hamartomatous syndrome
C. MYH-associated polyposis
FAP is autosomal dominant
Germline pathogenic variants in the MUTYH gene are associated with autosomal recessive (AR) MYH-associated adenomatous polyposis (MAP). With the absence of family history in MAP and the high rate of de novo mutations in attenuated FAP and MAP (20%), both FAP and MAP are on the list of differential diagnoses.
A molecular hallmark of carcinomas caused by MUTYH deficiency is the presence of a specific somatic KRAS mutation, c.34G>T (G12C) in codon 12 in 64% of MAP CRCs, which does not appear in FAP
A 16-year-old male was referred to a genetics clinic for mild cognitive impairment with >1000 colorectal adenomatous polyps. Genetic evaluations uncovered that he also had mild dysmorphic features. The family history was unremarkable on both sides. The medical geneticist ordered a test to rule out genetic etiologies. Which one of the following genetic tests would be most appropriate for this patient?
A.Chromosome microarray
B.Methylation study of the APC gene
C.Sequence the APC gene
D.Sequence the MUTYH gene
E.Sequence APC and MUTYH genes
F.None of the above
Interstitial deletions of chromosome 5q22 that include APC have been reported in individuals with attenuated adenomatous polyposis and classic adenomatous polyposis. In all reports, such individuals have had cognitive impairment, usually in the mild-to-moderate range, and the majority had dysmorphic features
Normal FAP mutations have normal intelligence and appearance
Which one of the following genes associated with Lynch syndrome has more pseudogenes than the others?
A. BRAF
B. EpCAM
C. MLH1
D. MSH2
E. MUTYH
F. PMS2
F. PMS2
15 pseudogenes
MSI for CRC patient showed one of five mononucleotide polymorphisms were unstable. Immunohistochemistry (IHC) stains for MLH1, MSH2, PMS2, and MSH6 were done with the tumor tissue. The results showed staining for all four proteins. The patient met the clinical diagnosis for Lynch syndrome based on Amsterdam II Criteria. Which one of the following genes would most likely harbor a pathogenic variant in this patient?
A.BRAF
B.MLH1
C.MSH2
D.MSH6
E.PMS2
D.MSH6
Clinical diagnosis of juvenile polyposis was made. The medical geneticist ordered a molecular test for this patient. Which gene(s) listed would most likely be included in the genetic evaluations for this patient?
A.APC
B.BMPR1A
C.APC and BMPR1A
D.SMAD4
E.BMPR1A and SMAD4
F.STK11 G.APC and STK11
E.BMPR1A and SMAD4
20% BMPR1A and 20% SMAD4
A 13-year-old male patient was referred to a genetics clinic to rule out genetic etiologies for his recurrent GI bleeding, mucocutaneous telangiectases, and pulmonary arteriovenous malformations. His pediatric gastroenterologist found and had been able to control the polyps in the stomach and colon by upper endoscopy and colonoscopy. Histopathological evaluations of the lesions in the upper duodenum demonstrated high-grade dysplasia. Which one of the following analyses would most likely be used for the genetic evaluation to rule out genetic etiologies in this patient?
A.Chromosome karyotype
B.Microarray copy-number analysis
C.APC sequencing
D.BMPR1A sequencing
E.SMAD4 sequencing
F.STK11 sequencing
E.SMAD4 sequencing
Juvenile polyposis syndrome/Hereditary hemorrhagic telangiectasias with SMAD4
Upper GI juvenile polyps with colonic hamartomatous poyps with dysplasia. Developmental delay and macrocephaly. Which one of the following analyses would most likely be used for the genetic evaluation to rule out genetic etiologies in this patient?
A.Chromosome karyotype
B.Microarray copy-number analysis
C.APC sequencing
D.BMPR1A sequencing
E.SMAD4 sequencing
F.PTEN sequencing
B.Microarray copy-number analysis
10q22-q23 microdeletion syndrome with PTEN (Cowden - cognition and macrocephaly) and BMPR1A (JPS)
Juvenile patient with strong FHx of CRC and perioral and acral/oral freckles. What one of the following hereditary cancer predisposition syndromes may this patient have if he has one?
A.Familial adenomatous polyposis
B.Lynch syndrome
C.MYH-associated polyposis
D.Peutz–Jeghers syndrome
E.PTEN hamartomatous syndrome
D.Peutz–Jeghers syndrome
Histopathological examinations revealed hamartomatous polyps consistent with a clinical diagnosis of Peutz–Jeghers syndrome (PJS). Which gene(s) listed below would most likely be included in the genetic test for this patient?
A.APC
B.BMPR1A
C.APC and BMPR1A
D.SMAD4
E.BMPR1A and SMAD4
F.STK11
G.APC and STK11
F.STK11
19P13.3- STK11/LKB1
GI hamartomatous polyps and mucocutaneous hyperpigmentation
Histopathological examinations revealed hamartomatous polyps consistent with a clinical diagnosis of Peutz–Jeghers syndrome (PJS). Which one of the following represents the approximate detection rate of sequencing analysis of the STK11 gene in patients diagnosed with PJS clinically?
A.25%
B.50%
C.75%
D.99%
E.Unknown
B.50%
Molecular genetic tests detected a heterozygous pathogenic variant in the STK11 gene. A diagnosis of Peutz–Jeghers syndrome was made. Which one of the following cancers would the patient have highest risk of developing in her lifetime?
A.Brain tumor
B.Breast cancer
C.Cervical cancer
D.Melanoma
E.None of the above
B.Breast cancer
PJS highest risk for GI and breast cancer
A microarray copy-number analysis was ordered for a 4-year-old girl with autism. The results revealed a 324-kb deletion on 19p13.3, including the STK11 gene. What would be the clinical significance of this finding?
A.Pathogenic
B.Unknown clinical significance, likely pathogenic C.Unknown clinical significance
D.Unknown clinical significance, likely benign
E.Benign
A.Pathogenic
Even if not related to autism - although some evidence deletion can be associated with autism
43 yo with bilateral BRCA, macrocephaly and FHx of endometrial, RCC and “neck” cancer. Which one of the following hereditary cancer predisposition syndromes would this patient most likely have if she had one?
A.Familial adenomatous polyposis
B.Lynch syndrome
C.MYH-associated polyposis
D.Peutz–Jeghers syndrome
E.PTEN hamartomatous tumor syndrome
E.PTEN hamartomatous tumor syndrome
Cowden syndrome (CS) is a type of PTEN hamartomatous tumor syndrome. Affected individuals usually have macrocephaly (>97th percentile head circumference), trichilemmomas, and papillomatous papules. The lifetime risk of developing benign and malignant tumors of the thyroid, breast, and endometrium is increased significantly.
43 yo with bilateral BRCA, macrocephaly and FHx of endometrial, RCC and “neck” cancer. Which one of the following gene-sequencing tests would be the most appropriate first-tier genetic evaluation for this patient?
A.BRAC1
B.BRAC2
C.BRAC1 and BRAC2
D.CDH1
E.PTEN
F.STK11
G.VHL
E.PTEN
A small-bowel segment was resected. Histopathological examinations revealed hamartomatous polyps. The family history was negative for both polyposis and cancers. A medical geneticist was called for consultation. Which one of the following genes would most likely NOT be sequenced in this patient to rule out genetic etiologies?
A.APC
B.BMPR1A
C.SMAD4
D.STK11
E.PTEN
A.APC
Histopathological examinations revealed hamartomatous polyps. The family history was negative for both polyposis and cancers. A medical geneticist was called for consultation. Which one of the following gene panels would be the most appropriate first-tier genetic evaluation for this patient?
A.APC, MUTYH
B.BMPR1A, SMAD4, STK11, PTEN
C.MLH1, MSH2, MSH6, PMS2, PSM6
D.MUTYH, STK11, PTEN
E.All of the above
F.None of the above
B.BMPR1A, SMAD4, STK11, PTEN
**SMAD2 corrected to SMAD4
A colonoscopy revealed multiple and diffuse polyps, supporting the diagnosis of FAP. Which one of the following gene-sequencing tests would be the most appropriate first-tier genetic evaluation for this patient?
A.APC
B.BMPR1A
C.MLH1
D.MUTYH
E.None of the above
A.APC
5q21
The medical history revealed adenomatous polyposis at the age of 40 and CRC at the age of 56. His family history was unremarkable on both sides. The APC gene was sequenced, and the results were negative. Which one of the following gene-sequencing tests would be the most appropriate next step in the genetic evaluation for this patient?
A.BMPR1A
B.MLH1
C.MUTYH
D.SMAD4
E.PTEN
F.None of the above
C.MUTYH
MAP is an autosomal recessive adenomatous polyposis syndrome. Individuals with MAP usually have less adenomatous polyposis than patients with familial adenomatous polyposis (FAP), and they have an increased risk of colorectal cancer (CRC). The mean age at onset is about 50 years. Family history is usually negative.
Meng, Haiying. Self-assessment Questions for Clinical Molecular Genetics (p. 388). Academic Press. Kindle Edition.
A 10-year-old boy was diagnosed with adenomatous polyposis of the small intestine 2 weeks ago. A colonoscopy detected hundreds of polyposis. Histopathological examinations revealed adenomatous polyps. The family history was negative for both polyposis and cancers. A clinical geneticist was called for consultation. Which one of the following gene panels would be the most appropriate first genetic evaluation for this patient?
A.APC, MUTYH
B.BMPR1A, SMAD2, STK11, PTEN
C.MLH1, MSH2, MSH6, PMS2, PSM6
D.MUTYH, STK11, PTEN
E.All of the above
F.None of the above
A.APC, MUTYH
How frequently do patients with breast cancer(s) have predisposition mutations in the BRCA1 or BRCA2 gene?
A.<1%
B.5%–10%
C.15%
D.20%–25%
E.40%
B.5%–10%
How frequently do patients with hereditary breast cancer(s) have predisposition mutations in the BRCA1 or BRCA2 gene?
A. <1%
B. 5%–10%
C. 15%
D. 20%–25%
E. 40%
***B.5%–10%
A 58-year-old Caucasian female was diagnosed with triple-negative multifocal breast cancer. Her medical history was significant for ovarian cancer diagnosed at age 52. Which one of the following genetic tests would be appropriate for this patient?
A. BRCA2 sequencing
B. BRCA1 sequencing
C.BRCA1 and BRCA2 sequencing
D. HER2 FISH
E. STK11 sequencing
F. PTEN sequencing
***C.BRCA1 and BRCA2 sequencing
A 28-year-old Caucasian female was diagnosed with triple-positive right breast cancer. Which one of the following genetic tests would be appropriate in this patient?
A. BRCA2 sequencing
B. BRCA1 sequencing
C.BRCA1 and BRCA2 sequencing
D. HER2 FISH
E. HER2 sequencing
F. PTEN sequencing
***C.BRCA1 and BRCA2 sequencing
A biopsy of the breast mass confirmed the diagnosis of triple-negative breast cancer. The family history was positive for a paternal aunt who died of breast cancer and a cousin who was diagnosed with breast cancer at age 36. BRCA1 and BRCA2 tests were ordered for this patient, and the result was negative. Which one of the following genes will NOT be considered in the next step in the workup to rule out genetic etiologies?
A. ATM
B. CDH1
C. CHEK2
D. PALB2
E. PTEN
F. STK11
G. TP53
H. VHL
I.All of the above
J.None of the above
***H. VHL
Prenatal AJ testing. Targeted molecular tests were ordered and pathogenic variants in the BRCA2 gene were detected in both parents. Which one of the following disorders would the couple’s children be at risk of developing besides breast cancer?
A. Ataxia telangiectasia
B. Bloom syndrome
C. Fanconi anemia
D. Hereditary telangiectasia
E. Nijmegen breakage syndrome
F.All of the above
G.None of the above
***C. Fanconi anemia
biallelic BRCA2 mutations
Prenatal AJ testing. Targeted molecular tests were ordered and pathogenic variants in the BRCA2 gene were detected in both parents. If their firstborn child developed Fanconi anemia, which one of the following genes would most likely harbor a pathogenic variant in both parents?
A. BRCA1
B. BRCA2
C. PTEN
D. TP53
E. VHL
***B. BRCA2
Preconception counseling. Molecular tests were ordered, and pathogenic variants in the BRCA1 gene were detected in both the husband and the wife. Which one of the following disorders would the couple’s children be at risk of developing besides breast cancer?
A. Ataxia telangiectasia
B. Bloom syndrome
C. Fanconi anemia
D. Hereditary telangiectasia
E. Nijmegen breakage syndrome
***C. Fanconi anemia
43-year-old female came to a genetics clinic because she was recently diagnosed with breast cancer. Her family history was significant for adrenocortical carcinoma, breast cancer, and osteosarcoma. Which one of the following genetic conditions would most likely be consistent with the clinical presentations in this family?
A.Cowden syndrome
B.Hereditary breast and ovarian cancer
C.Li–Fraumeni syndrome
D.Multiple endocrine neoplasia type 1 (MEN1)
E.Multiple endocrine neoplasia type 2 (MEN2)
F.von Hippel–Lindau
C.Li–Fraumeni syndrome
Li–Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome associated with the development of soft tissue sarcoma, osteosarcoma, premenopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias.
43-year-old female came to a genetics clinic because she was recently diagnosed with breast cancer. Her family history was significant for adrenocortical carcinoma, breast cancer, and osteosarcoma. Which one of the following genes should be analyzed first to confirm/rule out genetic etiologies in this family?
A.BRCA1
B.BRCA2
C.PTEN
D.TP53
E.VHL
D.TP53
A 15-year-old male was diagnosed with pheochromocytoma. History of left kidney resection for multiple focal clear-cell renal-cell carcinomas at age 10. Which one of the following genetic tests would be most appropriate for this patient to rule out genetic etiologies?
A.Sequencing reflex to del/dup analysis of RET
B.Sequencing reflex to del/dup analysis of SDHB C.Sequencing reflex to del/dup analysis of SDHD D.Sequencing reflex to del/dup analysis of VHL
E.None of the above
D.Sequencing reflex to del/dup analysis of VHL
hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear-cell renal-cell carcinoma; pheochromocytoma, pancreatic cysts and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts. Germline pathogenic variants in the VHL gene on 3p25.3 is the only gene associated with VHL.
A 17-year-old male was diagnosed with multifocal pheochromocytoma. The medical and family history was unremarkable. Which one of the following genetic tests would NOT be appropriate for this patient to rule out genetic etiologies?
A.Sequencing reflex to del/dup analysis of RET B.Sequencing reflex to del/dup analysis of SDHB C.Sequencing reflex to del/dup analysis of SDHD D.Sequencing reflex to del/dup analysis of TP53 E.Sequencing reflex to del/dup analysis of VHL
D.Sequencing reflex to del/dup analysis of TP53
Approximately 25% of individuals with pheochromocytoma and no known family history of pheochromocytoma may have an inherited disease caused by a mutation in one of four genes: RET, VHL, SDHD, or SDHB. The recently discovered pheochromocytoma susceptibility genes TMEM127, MAX, and SDHA further expand the differential diagnosis for nonsyndromic paraganglioma and pheochromocytoma.
Approximately 25% of individuals with pheochromocytoma and no known family history of pheochromocytoma may have an inherited disease caused by a mutation in one of four genes: RET, VHL, SDHD, or SDHB. The recently discovered pheochromocytoma susceptibility genes TMEM127, MAX, and SDHA further expand the differential diagnosis for nonsyndromic paraganglioma and pheochromocytoma.
Her family history was significant for cerebellar hemangioblastomas, renal-cell carcinoma, and pheochromocytoma. Lily, her older sister, was diagnosed with pheochromocytoma at the age of 43. Lisa, her mother, was diagnosed with renal-cell carcinoma at the age of 46. Her maternal grandfather, Tom, died from cerebellar hemangioblastomas at the age of 56. Which one of the following genetic conditions would most likely be consistent with the clinical presentations in this family?
A. Cowden syndrome
B.Hereditary breast and ovarian cancer C. Li–Fraumeni syndrome
D.Multiple endocrine neoplasia type 1 (MEN1)
E.Multiple endocrine neoplasia type 2 (MEN2)
F. von Hippel–Lindau
F. von Hippel–Lindau
After consulting a medical geneticist, the physician ordered a next-generation sequencing (NGS) panel for pheochromocytoma. Which one of the following genes would NOT be expected in the NGS panel for this patient?
A.NF1
B.RET
C.SDHD
D.TP53
E.VHL
F.None of the above
D.TP53
Approximately 25% of individuals with pheochromocytoma and no known family history of pheochromocytoma may have an inherited disease caused by a mutation in one of four genes: RET, VHL, SDHD, or SDHB. The recently discovered pheochromocytoma susceptibility genes TMEM127, MAX, and SDHA further expand the differential diagnosis for nonsyndromic paraganglioma and pheochromocytoma.
Approximately 25% of individuals with pheochromocytoma and no known family history of pheochromocytoma may have an inherited disease caused by a mutation in one of four genes: RET, VHL, SDHD, or SDHB. The recently discovered pheochromocytoma susceptibility genes TMEM127, MAX, and SDHA further expand the differential diagnosis for nonsyndromic paraganglioma and pheochromocytoma.
family history was significant for cerebellar hemangioblastomas, renal-cell carcinoma, and pheochromocytoma (see the pedigree below). Lily, her older sister, was diagnosed with pheochromocytoma at the age of 43. Lisa, her mother, was diagnosed with renal-cell carcinoma at the age of 46. Her maternal grandfather, Tom, died from cerebellar hemangioblastomas at the age of 56. Which one of the following genes should be analyzed first to confirm/rule out genetic etiologies in this family?
A. BRCA1
B. BRCA2
C. PTEN
D. TP53
E. VHL
E. VHL
hemangioblastomas of brain, spinal cord, retina, renal cysts and CCRCC
pheochromocytoma, pancreatic cysts, and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts.
38-year-old female came to a genetics clinic because she was recently diagnosed with breast cancer. Her family history was significant for thyroid cancer, breast cancer, and endometrial carcinoma. Which one of the following genetic conditions would most likely be consistent with the clinical presentations in this family?
A.Cowden syndrome
B.Hereditary breast and ovarian cancer
C.Li–Fraumeni syndrome
D.Multiple endocrine neoplasia type 1 (MEN1)
E.Multiple endocrine neoplasia type 2 (MEN2)
F.von Hippel–Lindau disease
A.Cowden syndrome
Cowden syndrome, caused by a germline pathogenic variant in PTEN, is a multiple-hamartoma syndrome with an increased risk for benign and malignant tumors of the thyroid, breast, and endometrium.
38-year-old female came to a genetics clinic because she was recently diagnosed with breast cancer. Her family history was significant for thyroid cancer, breast cancer, and endometrial carcinoma. Which one of the following genes should be analyzed first to rule out genetic etiologies in this family?
A.BRCA1
B.BRCA2
C.PTEN
D.TP53
E.VHL
C.PTEN
A pathogenic variant was detected in the PTEN gene, which was known to cause the PTEN hamartoma tumor syndrome (PHTS). Which one of thyroid cancers would most likely the members of this family have?
A.Anaplastic thyroid cancer
B.Follicular thyroid cancer
C.Medullary thyroid cancer
D.Papillary thyroid cancer
E.None of the above
B.Follicular thyroid cancer
Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age at diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer is approximately 35%. The risk for endometrial cancer may approach 28%. PTEN is the only gene in which pathogenic variants are known to cause PHTS. The most common type of thyroid cancer in individuals with PHTS is follicular, rarely papillary, but never medullary thyroid cancer
A pathogenic variant was detected in the PTEN gene, which was known to cause the PTEN hamartomatous tumor syndrome (PHTS). Which one of thyroid cancers would most likely the members of this family NOT have?
A. Anaplastic thyroid cancer
B. Follicular thyroid cancer
C. Medullary thyroid cancer
D. Papillary thyroid cancer
E.None of the above
C. Medullary thyroid cancer
The PTEN hamartoma tumor syndrome (PHTS), including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome. CS is a multiple-hamartoma syndrome with an increased risk for benign and malignant tumors of the thyroid, breast, and endometrium. Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age at diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer is approximately 35%. The risk for endometrial cancer may approach 28%. PTEN is the only gene in which pathogenic variants are known to cause PHTS. The most common type of thyroid cancer in individuals with PHTS is follicular, rarely papillary, but never medullary thyroid cancer
Which of the following genes would most likely be included in the genetic test to rule out dyskeratosis congenita a patient with AD inheritance pattern?
A.DKC1, TERC, and TINF2
B.TERC, TINF2, and TERT
C.TERT, NHP2, and NOP10
D.TINF2, TERT, and NHP2
B.TERC, TINF2, and TERT
AD = TERT, TERC, ACD,
DKC1 (Dyskerin 1): X-linked recessive inheritance
TERT (Telomerase Reverse Transcriptase): Autosomal dominant or recessive inheritance
TERC (Telomerase RNA Component): Autosomal dominant or recessive inheritance
TINF2 (Telomere Repeat Binding Factor 2): Autosomal recessive inheritance
ACD (Acyl-CoA Dehydratase): Autosomal dominant inheritance
CTC1 (Conserved Telomere Protein 1): Autosomal recessive inheritance
NHP2 (Non-Homologous End Joining Protein 2): Autosomal recessive inheritance
The medical geneticist suspected that the patient had Rubinstein–Taybi syndrome (RTS). Which one of the following genetic assays would be the most appropriate initial test for this patient?
A.Chromosome breakage study
B.Chromosome microarray
C.Methylation study
D.Multicolor flow cytometry FISH (flow-FISH) E.Sequencing
F.None of the above
E.Sequencing
40-50% CREBBP and 3-8% EP300 genes
10% microdeletions FISH
The medical geneticist suspected that the patient had Rubinstein–Taybi syndrome (RTS). In the genetic counseling session, the counselor mentioned that mutations in two genes have been known to cause RTS. How likely would sequencing analyses of both genes detect the pathogenic variant in this patient if he had RTS?
A.20%
B.50%
C.80%
D.99%
E.Unknown
B.50%
A molecular sequencing test was ordered, and the results turned out to be negative. The medical geneticist still suspected RTS in this patient, especially since the detection rate of sequencing analysis of the two genes is only approximately 50%. Which one of the following genetic assays would be most appropriate to further rule out RTS in this patient?
A.Chromosome breakage study
B.Chromosome karyotype
C.Chromosome microarray
D.Methylation study
E.Multicolor flow cytometry FISH (flow-FISH)
F.None of the above
C.Chromosome microarray
rule out microdeletions involving CREBBP and/or EP300 in this patient.
Sequencing confirms xeroderma pigmentosum (XP) in a 2yo boy. The mother is pregnant and she wants to find out how likely it will be for her unborn child to have the same condition. What is the estimated recurrent risk of this condition in siblings?
A.<1%
B.25%
C.50%
D.50% in brothers
B.25%
Xeroderma pigmentosum (XP) is AR is caused by mutations in at least nine genes, all involved in nucleotide excision repair (NER). These genes are XPA, XPC, DDB2, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and POLH.
The dermatologist suspects that the patient has xeroderma pigmentosum (XP), and a sequencing assay confirms the diagnosis. Which one of following cancers will have increased incidence in this XP patient?
A.Basal-cell carcinoma
B.Gastric carcinoma
C.Leukemia
D.Lung cancer
E.Melanoma
F.Squamous-cell carcinoma
G.All of the above
G.All of the above
45% SCC or BCC
5% SKCM
10-50X risk for brain, leukemia, lung, gastric tumors
The dermatologist suspects that the patient has xeroderma pigmentosum (XP), and a sequencing assay confirms the diagnosis. Which one of following cancers will most likely develop in this patient with XP?
A.Brain cancer
B.Gastric carcinoma
C.Leukemia
D.Lung cancer
E.Skin cancer
F.All of the above
E.Skin cancer
45% SCC or BCC
5% SKCM
What is expected to be the most characteristic DNA damage after exposure UV light in this patient with XP? A. AA dimer
B. TT dimer
C. CpG island
D. Double strand breakage
E. Single strand breakage
B. TT dimer
A 4-year-old boy is referred to a surgeon for an abdominal mass found by ultrasound. He is apparently healthy otherwise. After surgical removal of part of the left kidney, the boy is diagnosed with unilateral and unicentric Wilms tumor. The family history is unremarkable. Molecular genetic tests of the WT1 gene and chromosome microarray analysis are negative. Genetic test for Beckwith–Wiedemann syndrome is negative, too. The parents ask for the estimated recurrent risk for their next child, since the mother is currently pregnant. Which one of the following is the empiric risk of Wilms tumor to the unborn child?
A.50%
B.25%
C.6%–7%
D.<1%
E.None of the above
D.<1%
Nonsyndromic Wilms tumor most frequently occurs as a single occurrence in a family. Empiric risks to the sibs of a proband who represents a simplex case are unknown but likely low (up to 1%)
A germline pathogenic variant in the WT1 gene is thought to be the cause of about 10%–15% of Wilms tumors.
The gyral enhancement in right parieto-occipital region was suggestive of angiomatosis. Which one of the following genetic assays would most likely be used for the genetic evaluation to confirm/rule out genetic etiologies in this patient?
A.Chromosome karyotype
B.Chromosome microarray
C.Methylation study
D.Multicolor flow cytometry FISH (flow-FISH) E.Sequencing
F.Targeted-mutation analysis
G.None of the above
B.Chromosome microarray
11p13 deletion of PAX6 (eye and brain) and WT1(Wilms and GU)
A fellow in a clinical molecular genetic laboratory works on a project to develop a next-generation sequencing (NGS) panel for Cowden and Cowden-like syndromes. Which one of the following genes should NOT be included in the panel?
A. PTEN
B. SDHB
C. SDHC
D. SDHD
E. VHL
F.None of the above
E. VHL
Cowden-like syndrome may be caused by KLLN promoter hypermethylation, pathogenic variants in SDHB, SDHC, SDHD, or in PIK3CA and AKT1
The pathological examination of a biopsy of the cysts confirmed the diagnosis of pleuropulmonary blastoma. His family history was remarkable for his father having multinodular goiter and a paternal aunt having ovarian Sertoli–Leydig cell tumor. The physician suspected that the patient had a hereditary cancer syndrome. Which one of the following hereditary cancer predisposition syndromes would this patient most likely have?
A. DICER1 syndrome
B. Gorlin syndrome
C. Li–Fraumeni syndrome
D.PTEN hamartomatous tumor syndrome
E. Xeroderma pigmentosum
F.None of the above
A. DICER1 syndrome
DICER1 gene, autosomal dominant inheritance which provides instructions for making a protein that is involved in the production of microRNA (miRNA)
18 mo with pleuropulmonary blastoma. Which one of the following genes would most likely be sequenced to rule out genetic etiologies in this patient?
A. DICER1
B. ERCC2
C. RET
D. PTEN
E. TP53
F.None of the above
A. DICER1
Patient with pleuropulmonary blastoma and FHx multinodular goiter and Sertoli-Leydig tumor. Which one of the following genes would be the most appropriate first-line genetic workup to rule out genetic etiologies in this patient?
A. DICER1
B. ERCC2
C. RET
D. PTEN
E. TP53
F.None of the above
A. DICER1
Patient with pleuropulmonary blastoma and bilateral cystic nephroma and FHx multinodular goiter. Which one of the following malignancies would other family members have an increased risk of developing?
A. Breast cancer
B.Ovarian Sertoli–Leydig cell tumor
C. Parathyroid tumor
D. Pheochromocytoma
E. Renal-cell carcinoma
F.None of the above
B.Ovarian Sertoli–Leydig cell tumor
Pleuropulmonary blastoma (PPB), cystic nephroma, benign multinodular goiter, and ovarian sex-cord stromal tumors (Sertoli–Leydig cell tumor)
Less commonly observed tumors are ciliary body medulloepithelioma (CBME), botryoid-type embryonal rhabdomyosarcoma (ERMS) of the cervix or other sites, nasal chondromesenchymal hamartoma (NCMH), renal sarcoma, pituitary blastoma, and pineoblastoma
Patient with pleuropulmonary blastoma and bilateral cystic nephroma and FHx multinodular goiter and Ovarian Sertoli-Leydig cell tumor. Which one of the following assays would most likely be used for the genetic evaluation of pleuropulmonary blastoma for this patient?
A. Chromosome karyotype
B. Chromosome microarray
C. Methylation study
D.Multicolor flow cytometry FISH (flow-FISH)
E. Sequencing
F. Targeted-mutation analysis
G.None of the above
E. Sequencing
Sanger
Which one of the following malignancies would most likely be seen in this patient with Gorlin syndrome?
A. Breast cancer
B. Melanoma
C. Basal-cell carcinoma
D. Pheochromocytoma
E. Renal-cell carcinoma
F.None of the above
C. Basal-cell carcinoma
Which one of the following skin cancers is the most common in Caucasians?
A. Actinic keratosis
B. Basal-cell carcinoma
C. Dysplastic nevi
D. Melanoma
E. Squamous-cell carcinoma
F.None of the above
B. Basal-cell carcinoma
2nd is SCC
The results confirmed the patient had Gorlin syndrome. Which one of the following genes would most likely harbor a pathogenic variant in this patient if she had a genetic condition?
A. DICER1
B. ERCC2
C. PTCH1
D. PTEN
E. TP53
F. VHL
C. PTCH1
nevoid basal-cell carcinoma syndrome” (NBCCS). Approximately 60% of individuals have a recognizable appearance, with macrocephaly, bossing of the forehead, coarse facial features, and facial milia. Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet. In people with Gorlin syndrome, the type of cancer diagnosed most often is basal-cell carcinoma. In most individuals, the diagnosis of Gorlin syndrome is established using clinical diagnostic criteria. PTCH1 (formerly PTCH) and SUFU are the only genes in which mutations are known to cause Gorlin syndrome
The results confirmed the patient had Gorlin syndrome. From which one of the following brain tumors did the patient’s maternal uncle most likely die in his childhood?
A. Astrocytoma
B. Ependymoma
C. Glioblastoma
D. Medulloblastoma
E. Meningioma
F. Oligodendroglioma
D. Medulloblastoma
5% of affected individuals with Gorlin syndrome develop medulloblastoma during childhood.
Dyskeratosis congenita with bald tongue, brittle nails, photophobia, epiphora and pancytopenia. Which one of the following genes would most likely be included in the test ordered for the patient?
A. DICER1
B. ERCC2
C. FANCA
D. PTCH1
E. TERT
F. VHL
E. TERT
classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. Individuals with DC have an increased risk of developing several life-threatening conditions, such as bone-marrow failure, and pulmonary fibrosis. Approximately half of people with DC have heterozygous mutations in the TERT, TERC, DKC1, or TINF2
Xeroderma pigmentosum with bald tongue, brittle nails, photophobia, epiphora and pancytopenia. Which one of the following assays would be the most sensitive to confirm/rule out genetic etiologies in this patient?
A. Chromosome breakage study
B. Chromosome microarray
C.FISH for gene amplification
D. Next-generation sequencing
E. Telomere-length measurement
F.None of the above
E. Telomere-length measurement
Which one of the following hereditary syndromes is the most commonly seen in children with hepatoblastoma?
A. Beckwith–Wiedemann syndrome
B. Familial adenomatous polyposis
C. Gorlin syndrome
D. Li–Fraumeni syndrome
E.None of the above
A. Beckwith–Wiedemann syndrome
most are sporadic
15% from BWS»_space; FAP
Histological examinations confirm medullary carcinoma of the thyroid. There is no family history of thyroid cancer. Her mother died of complications of pheochromocytoma after a routine hysterectomy. She has two healthy children, 4 and 8 years old. Which one of the following hereditary cancer predisposition syndromes may be considered to rule out genetic etiologies in this patient?
A. Cowden syndrome
B. Familial adenomatous polyposis
C. Gorlin syndrome
D.Multiple endocrine neoplasms, type 1 (MEN1)
E.Multiple endocrine neoplasms, type 2 (MEN2)
F.All of the above
G.None of the above
E.Multiple endocrine neoplasms, type 2 (MEN2)
Medullary carcinoma and FHx of pheochromocytoma. Which one of the following genes may be tested to rule out genetic etiologies?
A. DICER1
B. MEN1
C. PTEN
D. RET
E. TP53
F. VHL
D. RET
Which one of the following thyroid cancers does the patient most likely have if she has multiple endocrine neoplasia type 2 (MEN2)?
A. Anaplastic thyroid cancer
B. Follicular thyroid cancer
C. Medullary thyroid cancer
D. Papillary thyroid cancer
E.None of the above
C. Medullary thyroid cancer
Mucosal neuromas and pheochromocytoma. Which one of the following hereditary cancer predisposition syndromes would be considered to rule out genetic etiologies in this patient?
A. Cowden syndrome
B. Familial adenomatous polyposis
C. Gorlin syndrome
D.Multiple endocrine neoplasms, type 1 (MEN1)
E.Multiple endocrine neoplasms, type 2 (MEN2)
F.All of the above
G.None of the above
E.Multiple endocrine neoplasms, type 2 (MEN2)
MEN2B
Mucosal neuromas and pheochromocytoma. Histopathological examinations confirmed the diagnosis of pheochromocytoma. Which one of the following genes may be tested to rule out genetic etiologies in this patient?
A. DICER1
B. MEN1
C. PTEN
D. RET
E. TP53
F. VHL
D. RET
Diagnosis of a well-differentiated neuroendocrine tumor-secreting gastrin. A CT scan of the abdomen identified multiple foci in the pancreas. Later she was again sent to surgery for adhesive intestinal obstruction. Her family history was significant for one of her maternal aunts having a parathyroid tumor. The physician suspected that the patient had a hereditary cancer syndrome. After consulting with a medical geneticist, the physician ordered a molecular test for the patient. Which one of the following hereditary cancer predisposition syndromes might be considered to rule out genetic etiologies in this patient?
A. Cowden syndrome
B. Familial adenomatous polyposis
C. Gorlin syndrome
D.Multiple endocrine neoplasms, type 1 (MEN1)
E.Multiple endocrine neoplasms, type 2 (MEN2)
F.All of the above
G.None of the above
D.Multiple endocrine neoplasms, type 1 (MEN1
Patient with pancreatic NET and FHx parathyroid adenoma. Which one of the following genes would most likely be sequenced for this patient to rule out genetic etiologies?
A. DICER1
B. MEN1
C. PTEN
D. RET
E. TP53
F. VHL
B. MEN1
Patient with pancreatic NET and FHx parathyroid adenoma. Which one of the following assays would be most appropriate to confirm/rule out genetic etiologies in this patient?
A. Chromosome breakage study
B. Chromosome microarray
C. Methylation study
D. Next-generation sequencing
E. Sanger sequencing
F. Targeted-mutation analysis
G. Telomere-length measurement H.None of the above
E. Sanger sequencing
Which one of the following malignancies is NOT characteristic for multiple endocrine neoplasia syndrome type 1 (MEN1)?
A. Adrenocortical tumors
B. Carcinoid tumors
C. Medullary thyroid cancer
D. Pancreatic tumors
E.Parathyroid tumors with endocrinopathy
F. Pituitary tumors
G.All of the above
H.None of the above
C. Medullary thyroid cancer
Which one of the following genes is associated with multiple endocrine neoplasia syndrome type 1 (MEN1)?
A. BRAF
B. KRAS
C. MEN1
D. NRAS
E. PTEN
F. RB1
G. RET
H.None of the above
C. MEN1
Which one of the following malignancies is NOT one of characteristics of multiple endocrine neoplasia syndrome type 2 (MEN2)?
A. Medullary thyroid cancer
B. Mucosal neuroma
C. Pheochromocytoma
D. Pancreatic tumors
E. Parathyroid adenoma
F.All of the above
G.None of the above
D. Pancreatic tumors
Which one of the following genes is associated with multiple endocrine neoplasia syndrome type 2 (MEN2)?
A. BRAF
B. KRAS
C. MEN1
D. NRAS
E. PTEN
F. RET
G. RB1
H.None of the above
F. RET
Which one of the following genes is associated with familial medullary thyroid carcinomas?
A. BRAF
B. KRAS
C. MEN1
D. NRAS
E. PTEN
F. RET
G. RB1
H.None of the above
F. RET
How often are medullary thyroid carcinomas inherited?
A. <1%
B. 5%
C. 25%
D. 50%
E. 75%
C. 25%
Which one of the following syndromes is NOT associated with an increased risk for Wilms tumor?
A. Beckwith–Wiedemann (BWS)
B. Denys–Drash syndrome (DDS)
C. Neurofibromatosis type 1
D. Simpson–Golabi–Behmel syndrome (SGBS)
E. Trisomy 18
F. WAGR syndrome
G.None of the above
C. Neurofibromatosis type I
Developmental delay and café au lait spots. Which one of the following HCPSs might be considered to rule out genetic etiologies in this family?
A. Denys–Drash syndrome
B. Neurofibromatosis type 1
C. Neurofibromatosis type 2
D. Tuberous sclerosis
E.All of the above
F.None of the above
B. Neurofibromatosis type 1
Developmental delay and café au lait spots. Which one of the genes would most likely be sequenced to rule out genetic etiologies in this patient?
A. NF1
B. NF2
C. TSC1
D. TSC2
E. WT1
F.None of the above
A. NF1
Which one of the following symptoms is NOT likely manifested in individuals with neurofibromatosis type 1 (NF1)?
A. Acoustic schwannoma
B. Axillary freckling
C. Cutaneous neurofibromas
D. Lisch nodules
E. Malignant peripheral-nerve-sheath tumor
F. Optic-pathway tumor
A. Acoustic schwannoma
Bilateral acoustic masses. Which one of the following hereditary cancer predisposition syndromes would be considered to rule out genetic etiologies in this family?
A. Denys–Drash syndrome
B. Neurofibromatosis type 1
C. Neurofibromatosis type 2
D. Tuberous sclerosis
E.All of the above
F.None of the above.
C. Neurofibromatosis type 2
Bilateral acoustic masses and facial nerve (CN VII) palsy. Which one of the following genes would most likely be sequenced to rule out genetic etiologies in this family?
A. NF1
B. NF2
C. TSC1
D. TSC2
E. WT1
F. None of the above
B. NF2
Bilateral acoustic masses. Which one of the following conditions would most likely cause hearing loss in this patient?A. Astrocytomas
B. Ependymoma
C. Meningioma
D. Neurofibromas
E. Schwannoma
F.All of the above
G.None of the above
E. Schwannoma
Bilateral acoustic masses. Which one of the following assays would most likely be used for the genetic test that the physician ordered for this patient?
A. Chromosome breakage study
B. Chromosome microarray
C. Methylation study
D. Next-generation sequencing
E. Sanger sequencing
F. Targeted-mutation analysis
G. Telomere-length measurement H.None of the above
E. Sanger sequencing
Sequencing analysis is estimated to identify up to 2/3 of the patients with NF2. Deletion/duplication analysis may detect approximately 20% of patients. So the total sensitivity of sequencing and deletion/duplication is about 90%
The physician suspected that the patient had hereditary pheochromocytoma. After consulting with a medical geneticist, the physician ordered a genetic test for the patient. Which one of the following assays would most likely be used for the genetic test that the physician ordered for this patient?
A. Chromosome breakage study
B. Chromosome microarray
C. Methylation study
D. Next-generation sequencing
E. Sanger sequencing
F. Targeted-mutation analysis
G. Telomere-length measurement H.None of the above
D. Next-generation sequencing
ten genes play an important role in the pathogenesis of pheochromocytomas: RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, SDH5, and TMEM127.
Meng, Haiying. Self-assessment Questions for Clinical Molecular Genetics (p. 423). Academic Press. Kindle Edition.
The physician suspected that the patient had hereditary pheochromocytoma. After consulting with a medical geneticist, the physician ordered a next-generation sequencing (NGS) panel for the patient. Which one of the following genes would most likely be included in the panel for hereditary form of pheochromocytoma to rule out genetic etiologies in this patient?
A. BRAF
B. KRAS
C. MEN1
D. NRAS
E. PTEN
F. SDHB
G.None of the above
F. SDHB
The physician suspected that the patient had hereditary pheochromocytoma. After consulting with a medical geneticist, the physician ordered a next-generation sequencing (NGS) panel for the patient. Which one of the following genes would most likely NOT be included in this panel for the hereditary form of pheochromocytoma to rule out genetic etiologies in this patient?
A. MEN1
B. NF1
C. RET
D. SDHB
E. SDHC
F. SDHD
G. VHL
H.None of the above
A. MEN1
Patient with bilatral intracranial schwannomas. physician suspected that the patient had hereditary pheochromocytoma. After consulting with a medical geneticist, the physician ordered a next-generation sequencing (NGS) panel for the patient. Which one of the following hereditary cancer predisposition syndromes would most likely this patient have if she had one?
A. Li–Fraumeni syndrome
B.Multiple endocrine neoplasia syndrome, type 1 (MEN1)
C. Neurofibromatosis type 1
D. Neurofibromatosis type 2
E. von Hippel–Lindau syndrome
F. Cowden syndrome
C. Neurofibromatosis type 1
**book says NF2 so I corrected it
When does retinoblastoma(s) usually occur in an individual?
A. Any age
B.Before 3 years of age
C.Before 5 years of age
D.Before 7 years of age
E.12 years of age
F.40 years of age
C.Before 5 years of age
A 2-year-old boy is brought to a clinic for bilateral retinoblastomas (Rb). What is the chance that the patient has a germline pathogenic variant in the RB1 gene?
A. >99%
B. 80%
C. 50%
D. 20%
E. <1%
A. >99%
After testing, the patient was diagnosed with bilateral retinoblastoma. After consulting with a medical geneticist, the physician ordered a sequencing-based test for the patient. Which one of the following genes would most likely be sequenced to rule out genetic etiologies in this patient?
A. GPC3
B. GPC4
C. RB1
D. RET
E. WT1
F.None of the above
C. RB1
The physician suspected that the patient had Noonan syndrome. After consulting a medical geneticist, the physician ordered a genetic test for the patient. Which one of the following assays would be most likely be used for the genetic test to rule out Noonan syndrome in this patient?
A. Chromosome breakage study
B. Chromosome microarray
C. Methylation study
D. Next-generation sequencing
E. Sanger sequencing
F. Targeted-mutation analysis
G. Telomere-length measurement H.None of the above
D. Next-generation sequencing
PTPN11 protein tyrosine phosphatase nonreceptor 11
RAS-MAPK pathway, such as SOS1, KRAS, NRAS, RAF1, BRAF, or MEK1
Which one of the following genes would most likely NOT be sequenced to rule out Noonan syndrome in this patient?
A. BRAF
B. HRAS
C. KRAS
D. NRAS
E. PTPN11
F. RAF1
G.All of the above
H.None of the above
B. HRAS
HRAS- Costello syndrome -intellectual disability, distinctive facial appearance, loose folds of skin, and heart problems
Cardiofaciocutaneous syndrome (CFC), Costello syndrome, multiple lentigines syndrome (also called “LEOPARD syndrome”), and Noonan syndrome are clinically overlapping conditions. Which one of the following pathways seems to be involved in the process of the pathogenesis of these syndromes?
A. Sonic hedgehog pathway
B. PI3K/Akt pathway
C. RAS/RAF pathway
D. Wnt signal pathway
E.All of the above
F.None of the above
C. RAS/RAF pathway
Girl and brother with depigmented hair and skin patches. Red fundus and blue irises. The physician suspected that the patient had a genetic condition. Which one of the following hereditary syndromes would the patient most likely have if she had a genetic condition?
A. Cardiofaciocutaneous syndrome (CFC) B. Costello syndrome
C. Noonan syndrome
D. Waardenburg syndrome
E.None of the above
D. Waardenburg syndrome
neural crest migration
PAX3: Responsible for Waardenburg syndrome types 1 and 3
MITF: Responsible for Waardenburg syndrome type 2
SNAI2: Responsible for Waardenburg syndrome type 2
SOX10: Responsible for Waardenburg syndrome type 4
EDN3: Responsible for Waardenburg syndrome type 4
EDNRB: Responsible for Waardenburg syndrome type 4
Waardenburg syndrome. After consulting a medical geneticist, the physician ordered a genetic test for the patient. Which one of the following genes would most likely be included in the genetic test for this patient?
A. PAX2
B. PAX3
C. PAX5
D. PXP6
E.All of the above
F.None of the above
B. PAX3
A physician suspected that the patient had Waardenburg syndrome. After consulting a medical geneticist, the physician ordered a genetic test for the patient. Which one of the following assays would most likely be used for the genetic test to rule out Waardenburg syndrome in this patient?
A. Chromosome breakage study
B. Chromosome microarray
C. Methylation study
D. Next-generation sequencing
E. Sanger sequencing
F. Targeted-mutation analysis
G. Telomere-length measurement H.None of the above
D. Next-generation sequencing
Ambiguous genitalia. An abdominal mass biopsy specimen confirmed the diagnosis of Wilms tumor. Histological evaluations biopsy specimen from the abdominal mass confirmed the diagnosis of Wilms tumor. The patient’s karyotype was 46,XY. The physician suspected that the patient had a genetic condition. Which one of the following hereditary syndromes would the patient most likely have?
A. Beckwith–Wiedemann syndrome
B. Denys–Drash syndrome
C. Frasier syndrome
D. Isolated Wilms tumor
E. WAGR syndrome
F.None of the above
B. Denys–Drash syndrome
Frasier syndrome is caused by a germline pathogenic variant in the WT1 gene, too. Frasier syndrome is characterized by focal segmental glomerulosclerosis in early childhood, but no increased risk for Wilms tumor. Males with Frasier syndrome have gonadal dysgenesis. Females with Frasier syndrome usually have normal genitalia.
Meng, Haiying. Self-assessment Questions for Clinical Molecular Genetics (p. 427). Academic Press. Kindle Edition.
An abdominal mass biopsy specimen confirmed the diagnosis of Wilms tumor. The patient’s karyotype was 46,XY. The physician suspected that the patient had a genetic condition. After consulting with a medical geneticist, the physician ordered a genetic test for the patient. Which one of the following genes would most likely provide an appropriate molecular diagnosis for this patient?
A. ALK
B. CDKN1A
C. PAX6
D. WT1
E.All of the above
F.None of the above
D. WT1
DDS
18 mo with Denys-Drash syndrome (DDS) and diffuse glomerulosclerosis, ambiguous genitalia and Wilms tumor? Which one of the following assays would most likely be used for the genetic test to rule out genetic etiologies in this patient?
A. Chromosome breakage study
B. Chromosome microarray
C. Methylation study
D. Next-generation sequencing
E. Sanger sequencing
F. Targeted-mutation analysis
G. Telomere-length measurement H.None of the above
E. Sanger sequencing
WT1
The physician suspected that the patient had Costello syndrome. After consulting a medical geneticist, the physician ordered a genetic test for the patient. Which one of the following genes would most likely provide an appropriate molecular diagnosis for this patient?
A. BRAF
B. HRAS
C. KRAS
D. NRAS
E. PTPN11
F. RAF1
G.All of the above
H.None of the above
B. HRAS
The physician suspected that the patient had Costello syndrome. Sequencing of the HRAS gene identified a pathogenic variant in this patient. Which one of the following cancers would this patient have an increased risk of developing in his lifetime?
A. Breast cancer
B. Colorectal cancer
C. Endometrial cancer
D. Melanoma
E. Neuroblastoma
F. Thyroid cancer
E. Neuroblastoma
15% lifetime risk of cancer
also rhabdomyosarcoma and urothelial cancer
The physician suspected that the patient had Costello syndrome. Sequencing of the HRAS gene identified a pathogenic variant in this patient. Which one of the following cancers would this patient have an increased risk of developing in his lifetime?
A. Breast cancer
B. Colorectal cancer
C. Endometrial cancer
D. Melanoma
E. Thyroid cancer
F. Transitional-cell carcinoma of the bladder
F. Transitional-cell carcinoma of the bladder
Which one of the following malignancies do patients with Birt–Hogg–Dubé syndrome (BHDS) have an increased risk of developing?
A. Breast cancer
B. Colorectal cancer
C. Endometrial cancer
D. Melanoma
E. Renal-cell carcinoma
F. Thyroid cancer
E. Renal-cell carcinoma
hybrid of oncocytoma and chromophobe histologic types
FLCN gene- AD inheritance - tumor suppressor
Which one of the following hereditary cancer predisposition syndromes is caused by activating mutations in a proto-oncogene but also can function as a tumor suppressor?
A. Birt–Hogg–Dubé syndrome
B. Li–Fraumeni syndrome
C.Multiple endocrine neoplasia type 1 (MEN1)
D.Multiple endocrine neoplasia type 2 (MEN2)
E. von Hippel–Lindau syndrome
F.All of the above
G.None of the above
D.Multiple endocrine neoplasia type 2 (MEN2)
*corrected from misprint of MEN1
Which one of the following hereditary cancer predisposition syndromes is caused by activating mutations in a proto-oncogene?
A. Birt–Hogg–Dubé syndrome
B. Costello syndrome
C.Li-Fraumeni syndrome
D. Multiple endocrine neoplasia type 1 (MEN1)
D.Neurofibromatosis type 1
E. von Hippel–Lindau syndrome
F.All of the above
G.None of the above
B. Costello syndrome
HRAS
*MEN1 corrected from MEN2 misprint
What are the four Amsterdan II criteria for Lynch syndrome
- At least 3 relatives
- one first-degree (parent, sibling, child) - Two successive generations
- One relative before age 50
- Exclude FAP
