Molecular oncogenesis and Angiogenesis

Question 1

Which oncogene, implicated in hormone-unresponsive breast cancer, can be treated with Trastuzumab?

Answer 1

HER2-Neu

Question 2

c-Kit is an example of what kind of oncogene

Answer 2

growth factor oncongene

Question 3

What is the most common oncogene family? What is the normal function of the gene product?

Answer 3

RAS - small GTPases involved in cell signal transduction

Question 4

K-RAS is commonly defective in what type(s) of cancer?

Answer 4

pancreas and colon

Question 5

H-RAS is commonly defective in what type(s) of cancer?

Answer 5

bladder and kidney

Question 6

c-ABL is implicated in what cancers? What is the genetic defect?

Answer 6

CML and ALL

t(9;22) balanced translocation

Question 7

C-MYC is implicated in what type of cancer?

Answer 7

Burkitt Lymphoma

Question 8

N-MYC is implicated in what type of cancer?

Answer 8

Childhood neuroblastoma

Question 9

Describe the normal function of the RB gene

Answer 9

Tumor suppressor gene: binds and suppresses E2F

Question 10

Describe the normal function of APC

Answer 10

Tumor suppressor gene

Normally helps destroy beta-catenin. Beta catenin normally activates TCF, a transcription factor promoting cell proliferation

Mutation of APC is associated with many adenomas

Question 11

What is Familial Adenomatous Polyposis (FAP)?

Answer 11

A form of cancer featuring 100’s of colon polyps

Caused by APC mutation

Question 12

What is Li-Fraumeni Syndrome?

Answer 12

Inherited mutation in the p53 gene, causing a 25x increased chance of cancer by age 50

Question 13

BAX is what type of protooncogene? BCL-2?

Answer 13

• Pro-apoptotic gene
• Anti-apoptotic gene

Question 14

What is CYPIAI and why is it clinically significant?

Answer 14

CYPIAI activates polycyclic aromatic hydrocarbons (PAHs), which are highly carcinogenic. 10% of caucasians have a highly-inducible form of CYPIAI which increases activation of PAHs and therefore increases risk of carcinogensis.

Question 15

What enzyme is responsible for detoxification of PAHs?

Answer 15

Glutathione-S-transferase

50% of caucasians have deletions in genes expressing this enzyme and therefore can’t effectively detoxify PAHs, increasing carcinogenic risk

Question 16

What are promoters? Give an example.

Answer 16

Promoters exacerbate (increase proliferation of) carcinogenic damage, but do not directly cause it.

Examples: hormones, alcohol.

Question 17

What is Xeroderma Pigmentosum?

Answer 17

A predisposition to skin cancer due to a defect in DNA nucleotide excision pathway (DNA repair)

Question 18

Name two general types of radiation damage and give some common cancers associated with each

Answer 18

1. Ionizing: thyroid, lung, breast, leukemia
2. UV: BCC, SCC, melanoma

Question 19

Burkitt Lymphoma is associated with what type of infection?

Answer 19

EBV

Question 20

Name the low-risk HPV types. Name the high-risk HPV types

Answer 20

• Low-risk: 6, 11
• High-risk: 16, 18, 31, 33

Question 21

What is the general mechanism for Hepatitis B oncogenesis?

Answer 21

HBx gene suppresses p53 (tumor suppressor) and activates growth factor expression

Question 22

What morphologic feature of tumor angiogenesis is a key driver of metastasis?

Answer 22

Cellular ‘holes’ in vasculature due to incomplete pericyte coverage of tumor vessels

Question 23

Describe the function of the following VEGF receptors:

1. VEGFR2
2. VEGFR3

Answer 23

1. vasculogenesis, angiogenesis
2. vasculogenesis, lymphangiogenesis

Question 24

Which VEGF receptor is primarily responsible for lymphangiogenesis?

Answer 24

VEGFR3

Question 25

What cell type do PDGF receptor inhibitors target? Why is this important?

Answer 25

pericytes

Removal of pericytes makes vessel endothelial cells more vulnerable to anti-VEGF therapy