FINALS: MOLECULAR ONCOLOGY

Question 1

study of tumors/neoplasm (growth of tissue that exceeds and is not coordinated with normal tissue).

Answer 1

Oncology

Question 2

not recurrent; suffix -oma to the tissue of origin

Answer 2

Benign

Question 3

invasive and tending to recur at multiple sites (cancer)

Answer 3

Malignant

Question 4

movement of tumor cells from the original (primary) site of the
tumor to other locations

Answer 4

Metastasis

Question 5

study of cancer at the molecular level

Answer 5

Molecular Oncology

Question 6

a term that includes
all malignant tumors.

Answer 6

CANCER

Question 7

CANCER:
an ABNORMAL MASS OF TISSUE that usually does not contain cysts or liquid areas

Answer 7

Solid tumors

Question 8

SOLID TUMORS CANCER:
tumor of EPITHELIAL TISSUE origin

Answer 8

Carcinoma

Question 9

SOLID TUMORS CANCER:
tumor of BONE, CARTILAGE, muscle, blood vessel, or fat

Answer 9

Sarcoma

Question 10

SOLID TUMORS CANCER:
- consists of multiple cell types
- Common among them is that they are capable of formation of ___________

Answer 10

Teratocarcinoma

• angiogenesis

Question 11

CANCER:
ABNORMAL CELLS in the blood grow out of control

Answer 11

Hematological malignancies

Question 12

Hematological malignancies CANCER:

• neoplastic disease of blood-forming tissue in which large number of WBCs populate the bone marrow and peripheral blood

Answer 12

Leukemia

Question 13

Hematological malignancies CANCER:

• neoplasm of lymphocytes that forms discrete tissue masses
  i. Usually accumulates in the lymph nodes
  ii. Purkitt’s lymphoma

Answer 13

Lymphoma

Question 14

• arise from terminally differentiated B cells
• abnormal plasma cells or cells from tumors in the bones/soft tissues of the body

Answer 14

Plasma cell neoplasms

Question 15

Cancer is caused by ________ mutations in DNA affecting 2 types of genes that control the cell division cycle and cell survival: ONCOGENES AND TUMOR SUPPRESSOR GENES

Answer 15

nonlethal mutations

Question 16

• Promote cell division
• Include cell membrane receptors that are
  bound by growth factors, hormones, and
  other extracellular signals
• Support cell survival by inhibiting apoptosis
• > 100 in the human genome
• Gain-of-function mutations resulting from
  ○ Amplification /translocation of DNA regions containing genes
  ○ Activating mutations that cause aberrant activity of the proteins

Answer 16

ONCOGENES

Question 17

• Factors that control transcription/translation of genes required for cell division
• Participate in repairing DNA damage and in
  promoting apoptosis
• Slow down/stop cell division by counteracting the movement of the cell from G1-to S (G1
  checkpoint) or G2 to M phase (G2 checkpoint)
• > 30 in the human genome
• Loss-of-function mutations
  ○ Inactivation of the gene products (deletion, translocation, mutation of the genes)
  ~ Ex. p53

Answer 17

Tumor-suppressor genes

Question 18

ANALYTICAL TARGETS OF MOLECULAR TESTING
- Molecular characteristics of the tissue from which a tumor arose
- Detection and monitoring the presence of
tumor
○ Abnormal amounts or locations of DNA, RNA, proteins and other
molecules from these targets
○ Examples: DNA & RNA from
a. CYTOKERATIN genes from gastric cancer
b. CARCINOEMBRYONIC ANTIGEN in breast cancer

Answer 18

Tissue-Specific Targets

Question 19

ANALYTICAL TARGETS OF MOLECULAR TESTING
- Genetic structures resulting from mutations in oncogenes and tumor-suppressor genes that are associated with tumor development
- Solid tumors, leukemias, lymphomas
- Mutated cell-free nucleic acid/circulating
tumor cells can be detected in blood and
other body fluids

Answer 19

Tumor-Specific Targets

Question 20

group of tumors arising from primitive neuroectodermal tissue

Diagnosis and prognosis:
1. cytogenetic methods
2. molecular methods:
RT-PCR, with amplification control
(GAPDH or 185 RNA)
on tissue/liquid biopsies

Answer 20

Ewing Sarcoma, EWS
(22q12)

Question 21

rare type of cancer of the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body

Detection methods:
1. FISH
2. RT-PCR
3. Semi-nested PCR
4. Agarose gel
electrophoresis & EtBr
staining (PCR product
detection)

Answer 21

SYNOVIAL SARCOMA
translocation, chrmosome 18 -Synopvial sarcoma, breakpoint 1 & 2, SYT-
SSX1, SYT-SSX2 t(X;18)
(p11.2;q11.2)

Question 22

most common soft tissue sarcoma of childhood (10% of all solid tumors in children)
➢ Alveolar RMS,
embryonal (RMS-E),
& primitive (RMS-P)all solid tumors in children)
➢ Alveolar RMS,
embryonal (RMS-E),
& primitive (RMS-P)

Detection methods: FISH, RT-PCR, qPCR, RNA
sequencing

Answer 22

Rhabdomyosarcoma (RMS)

Question 23

● Contraction & expansion of nucleotide repeat sequences in DNA
● Cause: dysfunction of 1 or more components of mismatch repair (MMR) systems

Answer 23

MICROSATELLITE INSTABILITY (MSI)

Question 24

recommended the screening of BAT25 & BAT26: & D5S346,
D25123, & D175250 for MSI determination

Answer 24

National Cancer Institute

Question 25

● Deletion/inactivation of a functional allele, leaving a mutated allele
● Detection methods:
○ PCR & capillary electrophoresis: amplification of heterozygous STR/VNTR loci
closely linked to the disease gene

Answer 25

LOSS OF HETEROZYGOSITY

Question 26

● A laboratory test done on a sample of blood (plasma/serum), urine, or other body fluid to
look for cells & nucleic acids released by the tumors into a person’s body fluids

Answer 26

LIQIOD BIOPSY

Question 27

● Series of intrachromosomal recombination events mediated by recombinase enzymes
that recognize specific sequences flanking the gene segments
● Very common in immune cells, especially lymphocytes

Answer 27

Gene Rearrangements

Question 28

Normal intrachromosomal breaking & joining of DNA in the genes coding for immunoglobulins and T-cell receptors

Answer 28

V(D)J recombination

Question 29

● Gene encoding the immunoglobulin
heavy chain is located on chromosome
14
● As B lymphocytes mature, selected
gene segments are joined together so
that the rearranged gene contains only
1 of each V (variable). D (diversity) & J
(joining) gene segments

Answer 29

Immunoglobulin heavy-chain gene rearrangement in B cells

Question 30

● Genes encoding the lg light chains:
kappa locus (chromosome 2) & lambda
locus (chromosome 22)
● Rearranged in a kappa-before-lambda
order

Answer 30

Immunoglobulin light-chain gene
rearrangement in B cells

Question 31

● T-cell receptor: 2 of 4 chains (α, β. γ &
δ) with characteristic structures
resembling Ig V. J. & C regions
○ α & δ chains: chromosome 14
○ Β & γ chains: chromosome 7
● V regions undergo gene
rearrangement by intrachromosomal
recombination
● V. (D). & J segments are joined
together with the addition/deletion
(trimming) of nucleotides at the
junctions between the gene segments

Answer 31

T-cell receptor gene rearrangement

Question 32

MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(14;18)(q32;q21)

Detection methods:
● Southern Blot
● PCR or qPCR with gel
electrophoresis or qPCR probe

Answer 32

Follicular lymphoma

Question 33

MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(11;14)(q13;q32)

Detection methods:
● Southern Blot
● PCR and RT-PCR
with gel/capillary
electrophoresis
● FISH or flow
cytometry analysis

Answer 33

Mantle cell lymphoma,
chronic lymphocytic
leukemia, B-prolymphocytic
Teukemia, plasma cell
leukemia, multiple myeloma,
splenic lymphoma

Question 34

MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(8:14)(q24:q11)

Detection methods
● Southern blot, using a 32p or digoxigenin-
labeled 1.4 kb Cla1-EcoR1 restriction
fragment
● Interphase FISH & CISH
● IHC: Myc protein
expression

Answer 34

Burkitt lymphoma

Question 35

MUTATIONS IN HEMATOLOGICAL MALIGNANCIES:
- t(15:17)(q22:q11.2-
q12)
- Fusion of the retinoic
acid receptor alpha
(RARA) gene on
chromosome 15 w/
the myelocytic
leukemia (MYL) gene
on chromosome 17

Detection Methods
● RT-PCR
● RT-qPCR

Answer 35

Promyelocytic
leukemia