Cancer genetics

Question 1

What is an oncogene?

Answer 1

A gain of function mutation that can activate pathways to promote cellular growth.

Question 2

What are the ways in which proto-oncogenes act as oncogenes?

Answer 2

1. Hyperactive protein made in normal amounts.
2. Normal protein made in hyper amounts.
3. A new gene is made due to chromosome fusion.

Question 3

What drug can be used against the Philadelphia chromosome (CML)?

Answer 3

Gleevec, an example of precision medicine!

Question 4

What is an oncomir?

Answer 4

miRNA that behave as oncogenes by inhibiting tumor suppressor genes. Extremely potent

Question 5

What is Ataxia Telandiectasia (A-T)?

Answer 5

A recessive chromosome instability syndrome that modulates cellular responses to DNA damage.

Question 6

What are the symptoms of A-T and when do they appear/

Answer 6

First signs appear around age 2: lack of balance, slurred speech. Progressively degenerates to radiosensitivity, immunodeficiency, and predisposition to cancer.

Question 7

What defect does radiation cause?

Answer 7

Double strand DNA break.

Question 8

Do XP patients have radiosensitivity?

Answer 8

No.

Question 9

What is a hallmark of A-T?

Answer 9

Chromosome restrictions on karyotype.

Question 10

What is Fanconi Anemia?

Answer 10

A recessive chromosome instability syndrome of a FA protein complex that modulates cellular response to DNA damage.

Question 11

What are symptoms of Fanconi Anemia?

Answer 11

Physical abnormalities (e.g. double thumb), bone marrow failure, malignancy

Question 12

What is Bloom syndrome?

Answer 12

A recessive chromosome instability syndrome. The bloom complex and the FA complex work together and fail to respond to DNA damage.

Question 13

What are the symptoms of Bloom syndrome?

Answer 13

Severe growth deficiency
Otitis media
Pneumonia
Infertility
Cancer

Question 14

What do you see on a Bloom karyotype?

Answer 14

Excessive crossing over

Question 15

What are 3 chromosome instability syndromes?

Answer 15

A-T
Franconi Anemia
Bloom Syndrome

Question 16

What is Knudson’s two hit hypothesis?

Answer 16

Developing a loss of function cancer requires a mutation of BOTH alleles.

Question 17

Is Rb dominant?

Answer 17

Yes, but incomplete penetrance

Question 18

What gene is mutated in Li Fraumeni syndrome?

Answer 18

p53

Question 19

Which BRCA gene can also cause male breast cancer?

Answer 19

BRCA2

Question 20

What does “expression profiling” get you?

Answer 20

Using a microarray, you can take a tissue and see what genes are expressed and how much.

Question 21

What is hierarchical clustering?

Answer 21

Grouping of experimental expression profiles according to similarity. Can do the whole genome at once.