Block 4 -- Tumor Suppressors and Apoptosis

Question 1

Characteristics of tumor suppressor genes:

Answer 1

1) recessive trait
2) protein product (usually inhibitory)
3) frequent target of oncogenic viruses

Question 2

What TSG is mutated in Retinoblastoma?

Answer 2

Rb

Question 3

What TSG is mutated in Li-Fraumeni syndrome?

Answer 3

p53

Question 4

What TSG is mutated in breast & ovarian cancer?

Answer 4

BRCA1 (early)

BRCA2 (late)

Question 5

What is the product of BRCA1/2? What is its function?

Answer 5

Nuclear protein

– functions in DNA replication to repair dsDNA breaks and DNA cross-links (G1/S)

Question 6

What is the product of p53? What is its function?

Answer 6

Transcription factor

• • DNA replication (S/G2)
• • responds to cellular stress to induce apoptosis

Question 7

What is the product of Rb?

Answer 7

Protein regulatory for cell cycle

– DNA replication (S/G2)

Question 8

What are the forms of retinoblastoma?

Answer 8

1) sporadic

2) familial

Question 9

How is Rb altered to cause retinoblastoma?

Answer 9

1) deletion

2) point mutation

Question 10

Knudson’s Two-Hit hypothesis was initially focused on which TSG?

Answer 10

Rb

Question 11

What happens in human colorectal cancers with regards to TSG?

Answer 11

p53 is deleted

Question 12

What is the cause of Li Fraumeni syndrome?

Answer 12

inherited p53 (point mutation in 248)
\+ accumulated mutations

Question 13

What cancers are involved in Li Fraumeni?

Answer 13

Multiple types of primary tumors

Question 14

Who studied human colorectal cancers, and it which population?

Answer 14

Fearon & Vogelstein

Ashkenazi Jewish

Question 15

Which TSG mutations are commonly involved in colorectal cancers?

Answer 15

Bcl-2

p53

Question 16

What are inherited BRCA mutations associated with?

Answer 16

familial breast & ovarian cancers

• • early adult onset
• • predisposition to multicentric & bilateral disease