Oncogenes and Tumor Suppressors

Question 1

Ras

Answer 1

oncogene; mutant Ras cannot be dephosphorylated by GAP = MAPK (MEK) signaling always on! =cell growth and proliferation

Question 2

ABL-BCR

Answer 2

oncogene once translocation occurs. der(9,22) = “Philadelphia chromosome” - drives CML.
Translocation causes uncontrolled upregulation of RTKs = cell growth and proliferation

Question 3

MYC-N

Answer 3

oncogene once amplified. MYC is a TF that when amplified increases transcription and thus cell growth and proliferation.
Example of intrachromosomal amplification. Amplification of MYCN is common in neuroblastomas

Question 4

BCl2

Answer 4

oncogene when translocated from Chr. 14 to Chr. 18 where it becomes under control of IgG promoter. = amplification of Bcl2 = overexpression = loss of apoptosis because Bcl2 binds Bax. Can cause MDR.

Question 5

HER2

Answer 5

oncogenic member of the epidermal growth factor receptor family, encoded by ERBB2. Amplified in some breast cancers which causes increased Ras-MAPK and AKT pathway signaling = cell growth, proliferation.
Can be inhibited by Herceptin or small molecule inhibs/ monoclonal antibodies

Question 6

PDGF

Answer 6

oncogene that increases growth signaling in glioblastomas

Question 7

MDM2

Answer 7

oncogene that is amplified as dmins in bone cancers, normally acts as a ubiquitin ligase for p53 so when amplified = loss of p53 = loss of apoptosis and loss of DNA repair = MDR and increased growth/proliferation and increased mutations

Question 8

cyclin D

Answer 8

oncogene when amplified as seen in breast and bladder cancers, amplification causes loss of RB function = loss of growth arrest between g1/s checkpoint = increased mutations, increased proliferation

Question 9

p53

Answer 9

tumor suppressor gene, loss of p53 = genomic instability, loss of DNA repair, loss of apoptosis = MDR, increased growth/proliferation, increased mutations, increased gene amplification.
Implicated in Li-fraumeni syndrome (LFS).

Question 10

RB

Answer 10

tumor suppressor gene, loss of both copies of RB alleles = loss of growth arrest function = increased transcription, increased mutations, increased growth/proliferation

Question 11

APC

Answer 11

tumor suppressor gene, loss of APC = increased beta-catenin = increased wnt signaling = cell proliferation.
Causes FAP (familial adenomatous polyposis) - colon cancer.

Question 12

2-HG

Answer 12

oncometabolite; mutant IDH converts a-KG to 2-HG instead of isocitrate. 2-HG causes gene silencing of tumor suppressors as well as decreased DNA repair = proliferation and mutations. Also has roles in immunosuppression. Seen in AML.

Question 13

BRCA1/2

Answer 13

tumor suppressor gene, mutant = loss of damaged DNA repair = increased mutations. Seen in breast, prostate, ovarian cancer.