Tumour genetics

Question 1

Which one of the following is not a hallmark of cancer:
1. Arises from a single cell
2. Genetic (not heritable)
3. Mutations accumulate over time
4. Tumours are heterogeneous
5.

Question 2

Proto-oncogenes promote ________ and will be ________ in cancer.

Answer 2

cell survival, constitutively activated.

Question 3

Tumour suppressor genes _______ apoptosis and ________ and will be knocked out.

Answer 3

promote, senescence

Question 4

What are the three mechanisms of how proto-oncogenes

Answer 4

1. Point mutation in gene–> Hyperactivity
2. Point mutation in regulatory region –> hyper-regulation
3. Gene gets amplified (paralogues are generated)

Question 5

Peto’s paradox states that the prevalence of cancer doesn’t correlate with the organism’s cell count. What does cancer prevalence correlate with?

Answer 5

Cancer prevalence is inversely proportional to the prevalence of p53.

Question 6

What’s the importance of RAS?

Answer 6

RAS is the second most downstream proliferation inducer. It weighs the net balance of multiple pathways and can activate Myc.

Question 7

What’s the importance of MYC?

Answer 7

There are c-myc and n-myc, these can be activated by MAX.

MAX can be repressed by MAD1, MAD3, MAD4, MXL1, MNT/ROX.

Question 8

What’s the angiogenic switch?

Answer 8

VEGFs, FGFs and EGFs stimulate angiogenesis. The cancer angiogenesis is non–hierarchical and will often generate perforated blood vessels. There are drugs to combat cancer angiogenesis, they often extend the asymptomatic cancer stage for 2-6 months.

The resistance is mediated by
1. The tumour growing large and hypoxic, making drug delivery difficult

2. The tumors may also adapt to become more aggressive in order to find blood supply from elsewhere.
3. Pericytes being recruited which modulate previously existing vasculature (alternative signalling to VEGFs/EGFs/FGFs).

Drugs
- VEGF, FGF, EGF antibodies
- Statins
- Thrombospondin-1

(read more if there’s time)

Question 9

I think this is a shitty argument, but some argue that you can’t look at cancer evolution from a darwinistic perspective due to three factors, which?

Answer 9

1. Fast evolutionary change gaining large advantages contradicts darwin’s idea that evolution is slow and iterative.
2. Tumours can mutate w/ neutral effect and remain, suggesting that the selection pressure of mutants aren’t due to selective pressure (BS ??)
3. The role of ageing stroma has led to genrealised theories of age-dependent carcinogenesis (?).