Cancer Genomics

Question 0

What are cancer’s acquired capabilities? What does cancer require?

Answer 0

1. Self-sufficiency in growth signals
2. Insensitivity to anti-growth signals like oncogenes or tumor suppressors
3. Evasion of apoptosis.
4. Limitless replicative potential (telomerases)
5. Tissue invasion/metastasis (spread of cancer from one organ to another)
6. Sustained angiogenesis. (Need blood supply)

Question 1

What is the difference between driver and passenger mutations?

Answer 1

Driver genes drive tumor growth and cell fate, cell survival, genome maintenance.
Passenger mutations confer no growth advantage and can occur thru replication errors.

Question 2

How can one mutation affect 2 processes?

Answer 2

1. Deletion in genes required for 2 processes
2. Hit regulatory gene (pleiotropic)
3. Translocation (super common in tumors)

Question 3

How do you distinguish between passenger and driver mutations?

Answer 3

Sequence many tumors!
Drivers should be enriched in tumors compared to control.
Drivers will have higher odds ratios or correlation to cancer.

Question 4

Is there evidence that some genes are mutated more than others in cancer?

Answer 4

Yes….genes commonly mutated in lung cancer were p53 and ras and egfr.

Question 5

Do different tumor types have different types of mutations?

Answer 5

Yes–some are common across many cancers.

No–some mutations Are specific to certain cancers

Question 6

Which are the common regions in ovarian cancer that are deleted or amplified and how can you tell?

Answer 6

Myc and ras are amplified.
RB is deleted.
Can tell by referencing to a control human genome. If a portion isn’t there then there is a deletion. If it’s overly amplified, there will be more of it.

Question 7

What is kataegis?

Answer 7

Hypothesis about how cancer mutations arise. It is thought to occur in clustered areas of hyper mutations. Not just one mutation at a time. Graph of mutations look like a cloud with rain falling. The rain is the cluster of mutations.

Question 8

How do you visualize and compare mutations in tumors?

Answer 8

Circle of chromosomes with point mutations and translocations mapped out.

Question 9

Do patterns of genomic instabilities differ between patients with same cancer?

Answer 9

Yes. Breast cancer for example: one patient has one genomic rearrangement and another has 100s.

Question 10

What is chromothripsis?

Answer 10

Chromosome shattering and reassembly…creates lots of genomic rearrangement. 2-3% of all cancers, 25% bone cancers