Cancer Genetics Flashcards Preview

CMBM E4 CB > Cancer Genetics > Flashcards

Flashcards in Cancer Genetics Deck (27):
1

Mechanisms of action of tumor suppressor genes

1. Regulate cell cycle
2. Regulate cell death
3. Repair DNA

2

What are the hallmarks of a tumor suppressor gene?

1. Loss of wildtype protein in tumor cells
2. Germline mutations increase cancer susceptibility
3. Loss of gene in animal model should confer cancer-prone phenotype (p53 null mice develop lymphomas)

3

Outcome of functional loss of a tumor suppressor depends upon _____ and _____

tissue / context

4

Retinoblastoma (Rb)

Autosomal dominant
Ubiquitously expressed tumor suppressor

5

How does Rb regulate cell cycle?

Binds E2F (transcription factor) ---> represses E2F-dependent transcription of cell cycle genes

6

What phosphorylates Rb?

CDKs

7

What cancers can be caused by mutation of Rb?

Retinoblastoma
Small cell lung cancer
Osteosarcoma

8

What cancers can be caused by phosphorylation of Rb?

Breast
Melanoma
Colon

9

What cancers can be caused by viral oncoprotein associated with Rb?

Cervical

10

DNA viruses can cause tumors via inactivation of which genes?

Rb and p53

11

T/F: Wild-type p53 is present in tumor cells

False. Only mutant p53 has been found in tumor cells.

12

Loss of wildtype p53 ---> _____

Tumors

13

What is the most frequently mutated gene in human cancers?

TP53

14

What regulates p53?

MDM2 binds p53 and inactivates it

15

Mechanisms of mutant p53 mutation

1. Bind DNA to alter gene expression
2. Bind to transcription factors to enhance their function
3. Form a complex with transcription factors to prevent their function
4. Interact with proteins to change their diversity

16

Which tumor suppressor functions in adhesion and signaling?

APC

17

What is one of the earliest events in colorectal cancer?

Loss of APC

18

BRCA mutations result in what?

Truncated proteins

19

How do mutations cause cancer?

They result in structural rearrangements of the protein so that the protein is continuously expressed (GAIN OF FUNCTION)

20

Describe the Ras point mutation.

Point mutations cause Ras to become GAP-insensitive (aka Ras cannot bind GAP) --> Ras is constitutively active / GTP is constitutively bound

21

What is gene amplification?

Expansion of gene copy number within the cell

22

Where is gene amplification frequently seen?

c-myc and erbB-2 (HER2) --> amplified in breast and ovarian cancers

23

Two mechanisms of chromosomal rearrangement

1. Transcriptional activation of proto-oncogenes
2. Creation of a fusion gene

24

What is an example of transcriptional activation caused by chromosomal rearrangement?

c-myc translocations in Burkitt's lymphoma
c-myc moved to locus of Ig heavy chain

25

What is an example of a fusion gene caused by chromosomal rearrangement?

Philadelphia chromsome
c-abl gene (9) fused to bcr gene (22)
causes increased kinase activity and abnormal cellular localization

26

Where are the majority of mutations in colorectal cancers found?

In three functional protein groups:

1. Cellular adhesion and motility (APC)
2. Signal transduction (APC)
3. Transcriptional regulation (Ras)

27

Which defect is seen in 90% of colon cancers?

Ras defect