CANCER- oncogenes and tumour suppressors

Question 1

what are the 6 hallmarks of cancer?

Answer 1

o Disregard signals to stop proliferating.

o Disregard signals to differentiate.

o Capacity for sustained proliferation.

o Evasion of apoptosis.

o Ability to invade.

o Ability to promote angiogenesis.

Question 2

what are the 4 hallmarks that were later added?

Answer 2

avoiding immune destruction

tumour promoting inflammation

genome instability and mutation

deregulating cellular energetics

Question 3

how can an oncogene be activated?

Answer 3

1. Mutation in the coding sequence.
   - ->Point mutation or deletion.
2. Gene amplification.
   - -> A protein may block the DNA polymerase so the polymerase repeatedly backs up to go over the area a few times creating many identical genes.
3. Chromosomal translocation.
   –>Chimeric genes.
   a strong promotor can be put infront of a gene that isnt usually well expressed and increases normal protein levels
4. Insertional mutagenesis.
   - -> Viral infections – some viruses insert their genome into our DNA and usually this isn’t a problem as much of our DNA does not code but if it’s in a coding region, this could be cancer.

Question 4

what do proto-oncogenes code for?

Answer 4

code for essential proteins involved in maintenance of cell growth, division and differentiation.

Question 5

what is the significance of RAS in tumour growth?

Answer 5

Upon binding GTP, RAS becomes active and it’s Dephosphorylation of GTPàGDP that switches RAS off

a mutant RAS fails to dephosphorylate GTP and remains active and bound to RAF and drives proliferation.

Question 6

what is a tumour suppressor gene?

Answer 6

TSGs encode proteins whose function is to regulate cellular proliferation and maintain cell integrity

Each cell has TWO copies of each TSG

Question 7

what are the features of cancer due to Tumour suppressor genes?

Answer 7

Family history of related cancers.

Unusually early age of onset.

Bilateral tumours in paired organs.

Synchronous or successive tumours.

Tumours in different organ systems in same individual.

Mutation inherited through the germline.

Question 8

what are the different functional classes of tumour suppressor genes?

Answer 8

Regulate cell proliferation

Maintain cellular integrity

Regulate cell growth

Regulate the cell cycle

Nuclear transcription factors

DNA repair proteins

Cell adhesion molecules

Cell death regulators