Lecture 23 - Cancer Genetics 1 (Hereditary Cancers)

Question 1

Many cancer-causing mutations target the _________, the period in G1 where cells commit to enter S phase.

Answer 1

restriction point

Question 2

Most cancers arise in _______ tissue from cells that have acquired a genetic change that leads to a selective growth advantage.

Answer 2

somatic

Question 3

The two key families of proteins responsible for regulating the cell cycle are:

Answer 3

1. cyclin-dependent kinases

2. cyclins

Question 4

The two families of CDK inhibitors include:

Answer 4

1. INK4 family

2. CIP/Kip family

Question 5

What happens when anti-proliferation genes are mutated?

Answer 5

Cell is released from the normal proliferation constraints and divides as a cancer cell.

Question 6

What mode of inheritance are mutations in anti-proliferation genes (also known as Tumor Suppressor Genes)?

Answer 6

recessive

Question 7

What mode of inheritance are mutations in oncogenes?

Answer 7

dominant

Question 8

Oncogenes are abnormally expressed or mutated forms of:

Answer 8

corresponding NORMAL CELLULAR proto-oncogenes

Question 9

Tumor suppressor genes are also known as:

Answer 9

anti-proliferation genes

Question 10

The most important cell-cycle checkpoints are found at what 3 timepoints:

Answer 10

1. G1/S
2. G2/M
3. M

Question 11

Proto-oncogenes may be integrated into a viral genome and are expressed at ________ levels than their cellular counterparts under the control of the viral promoter.

Answer 11

higher levels

Question 12

Tumor suppressor genes can cause cancer, but what must happen in the cell before it transforms to a cancerous state?

Answer 12

Both functional copies of the gene must be lost

Question 13

Proto-oncogenes may encode proteins that differ in structure and function from their normal cellular counterparts. What are 3 general reasons for this?

Answer 13

1. Mutations - premature truncation of protein or altered Amino Acid sequence
2. Fusion/translocation - form hybrid protein
3. Amplification - produce higher grade tumors

Question 14

In breast cancer, Her2 _________ are associated with a higher grade tumor.

Answer 14

amplification

Question 15

An important mechanism in TSG silencing is _________ of their promoters.

Answer 15

methylation

Question 16

The function of the Rb protein is primarily to:

Answer 16

restrict cell growth

Question 17

The Rb protein is regulated by:

Answer 17

phosphorylation

Question 18

The hypophosphorylated form of Rb protein binds E2F, a ____________ required for cell cycle entry, then does what?

Answer 18

binds to E2F transcription factor and prevents its entry

Question 19

______ is a tumor suppressor encoded by the TP53 gene that is altered/mutated in a majority of cancers.

Answer 19

p53 protein

Question 20

p53 is normally induced by:

Answer 20

DNA damage and cell stress

Question 21

Cells with a mutant p53 protein:

Answer 21

1. continue to replicate damaged DNA and

2. do not undergo apoptosis

Question 22

p53 is regulated by ________ modification, which alters its stability and function.

Answer 22

post-translational

Question 23

What is MDM2?

Answer 23

A oncogene that is a critical regular of p53 function; frequently amplified in sarcomas.

Question 24

A 55 year old man with a 40-year history of cigarette smoking is diagnosed with adenocarcinoma of the lung. A biopsy reveals that the tumor has a mutation in p53 and Ras. Which of the following statements about the genetic changes involved in cancer development is most accurate?

a) Tumor suppressor genes and oncogenes undergo loss-of-function mutations.
b) Tumor suppressor genes and oncogenes undergo gain-of-function mutations.
c) Tumor suppressor genes undergo gain-of-function mutations and oncogenes undergo loss-of-function mutations
d) Tumor suppressor genes undergo loss-of-function mutations and oncogenes undergo gain-of-function mutations.

Answer 24

D. TSG: Loss of function

Oncogenes: Gain of function

Question 25

Cyclins directly interact with:

A. pRB
B. Cyclin-dependent kinase inhibitors
C. Cyclin-dependent kinases
D. p53

Answer 25

C.