Oncogenes and tumor suppressors

Question 1

Platelet-derived growth factor B (PDGFB)

Answer 1

Proto-oncogene. Overexpressed in autocrine loop (comes back and stimulates cell that’s overproducing it) in astrocytoma, leading to overgrowth

Question 2

ERBB2/HER2/neu

Answer 2

Proto-oncogene. Epidermal growth factor receptor. Amplified in some breast carcinomas. Predicts treatment response to monoclonal antibody

Question 3

RET

Answer 3

Proto-oncogene. Neural growth factor receptor. Mutated in MEN2A, MEN2B, and in sporadic forms of medullary carcinoma. If suspect MEN2A or B and find RET mutation, then prophylactically remove thyroid to prevent medullary carcinoma

Question 4

KIT

Answer 4

Proto-oncogene. Stem cell growth factor receptor. Mutated in gastrointestinal stromal tumors

Question 5

RAS

Answer 5

Proto-oncogene. Signal transducer linked to growth factor receptor. When inactive bound to GDP; when GF binds receptor, GDP exchanged for GTP so Ras is active and can translocate to nucleus. GAP normally cleaves off one pohsphate to regenerate Ras-GDP and turn off signal. Overactive in many cancers including carcinomas, melanomas, and lymphomas

Question 6

ABL

Answer 6

Proto-oncogene. Signal transducer tyrosine kinase. t(9;22) translocation with BCR leads to overexpression in CML and some types of ALL (poor prognostic indicator)

Question 7

c-MYC

Answer 7

Proto-oncogene. Transcription factor that increases production of growth related proteins. Involved in t(8;14) translocation with IgH in Burkitt lymphoma. IgH on chromosome 14 is normally “on” in B cells, so translocation turns c-MYC on.

Question 8

N-MYC

Answer 8

Proto-oncogene. Trascription factor that increases production of growth related proteins. Amplified in neuroblastoma

Question 9

L-MYC

Answer 9

Proto-oncogene. Transcription factor that increases production of growth related proteins. Amplified in lung carcinoma - small cell

Question 10

Cyclin D1

Answer 10

Proto-oncogene. Cell cycle regulator. Translocation with IgH on chromosome 14 [t(11;14)] seen in mantle cell lymphoma

Question 11

CDK4

Answer 11

Proto-oncogene. Cell cycle regulator. Amplified in melanoma

Question 12

p53

Answer 12

Regulates progression from G1 to S phase. Looks for DNA damage and if mild, sends for DNA repair prior to progression to S; if severe, upregulates BAX which destroys Bcl2 which allows for cytochrome c to leak from the mitochondria, activate caspases, and cause apoptosis.

Question 13

Rb

Answer 13

Regulates progression from G1 to S by holding E2F TF, which is necessary for transition to S phase. E2F released when RB phosphorylated by cyclinD/CDK4 complex. Mutation in RB allows for constitutive expression of E2F and unregulated progresion through cell cycle.

Question 14

Familial retinoblastoma

Answer 14

Germline Rb mutation. Bilateral retinoblastoma + osteosarcoma

Question 15

BCL2

Answer 15

Regulator of apoptosis. Stabilizes mitochondrial membrane, blocking release of cytochrome c. Overexpressed in follicular lymphoma due to t(14;18), which moves Bcl2 on ch18 to Ig heavy chain locus on ch14. Results in super stable micochondrial membrane so that apoptosis doesn’t occur in the follicle, where it is an important part of somatic hypermutation.

Question 16

Telomerase

Answer 16

Upregulated in many cancers so that telomeres are preserved and senescence is avoided.

Question 17

Angiogenic factors

Answer 17

FGF and VEGF. Produced by many tumor cells to bring in new blood vessels and promote tumor survival.

Question 18

MHC class I

Answer 18

Production of abnormal proteins by tumor cell would normally call in CD8+ response. Tumor cells avoid immune surveillance by downregulating expression of MHC class I.