genetics 1: oncogenes + proto-oncogenes

Question 1

what are the 10 hallmarks of cancer?

Answer 1

1. self-sufficient
2. insensitive to anti-growth signals
3. anti-apoptotic
4. pro-invasive and metastatic
5. pro-angiogenic
6. non-senescent
7. dysregulated metabolism
8. evades immune system
9. unstable dna
10. inflammation

Question 2

what are proto-oncogenes?

Answer 2

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

Question 3

what are oncogenes?

Answer 3

proto-oncogenes that have mutated to produce proteins that no longer respond to control influences

• can be aberrantly expressed, over-expressed or aberrantly active

Question 4

how can oncogenes be activated?

Answer 4

• mutation in coding sequence
• gene amplification
• chromosomal translocation
• insertional mutagenesis

Question 5

what is Ras?

Answer 5

membrane bound GTPase produced by a proto-oncogene

- linked to cell proliferation

Question 6

when is Ras normally switched off and how does this differ with mutant Ras?

Answer 6

when ras dephosphorylates GTP -> GDP

- mutant Ras is unable to dephosphorylate and therefore remains active when it shouldn’t be

Question 7

what is the philadelphia chromosome?

Answer 7

translocation between chromosomes 9 & 22 -> fusion gene BCR-ABL1 -> BCR expressed more than it should be -> CML

Question 8

what are some examples of oncogenes and their associated tumours?

Answer 8

SRC (tyrosine kinase) -> breast, colon, lung
MYC (transcription factor) -> Burkitt’s lymphoma
JUN (transcription factor) -> lung
Ha-RAS (G-protein) -> bladder
Ki-Ras (G-protein) -> colon, lung