Tumor Suppressor Genes

Question 0

P53

Answer 0

Transcription factor for p21; blocks G1–> S phase

• p53 normally upregulates BAX which disrupts bcl-2 which allows leakage of cytochrome C from mt. and activates apoptosis
• both genes must be knocked out for tumor formation
• most human cancers and Li-Fraumeni syndrome(familial cancers of breast, brain, adrenal cortex, etc)

Question 1

Rb

Answer 1

Inhibits EF2; blocks G1–>S phase

EF2 is released when RB is hyperphosphorylated by cyclinD/CDK4 complex
-RB mutations result in constitutively free EF2 allowing progression thru the cell cycle and uncontrolled growth of cells
Sporadic mutation= unilateral RB
Germaine mutation= bilateral RB and OSTEOSARCOMA
(RB is on chromosome 13)

Question 2

BRCA1and BRCA2

Answer 2

DNA repair protein

-Breast and ovarian CA

Question 3

P16

Answer 3

Melanoma

Question 4

BRAF

Answer 4

Gene product is B-raf

- melanoma

Question 5

APC

Answer 5

Colorectal cancer (associated with FAP)

Question 6

WT1

Answer 6

Wilm’s tumor (nephroblastoma–>small round blue cell tumor)

Question 7

NF1

Answer 7

RAS GTPase activating protein (RAS-GAP)

-NeuroFibromatosis type 1

Question 8

NF2

Answer 8

Merlin (schwannomin) protein

-NeuroFibromatosis type 2

Question 9

DPC4

Answer 9

“Deleted in Pancreatic Cancer”

-pancreatic CA

Question 10

DCC

Answer 10

“Deleted in Colon Cancer”

-Colon CA

Question 11

Loss of function–> increased cancer risk

Answer 11

BOTH alleles must be lost for expression of disease