Lecture 13 - Oncogenes and tumour suppressor genes

Question 1

What is Rous carcinoma virus and what causes it?

Answer 1

Rous carcinoma virus is a viral oncogene that causes cancer.

Src gene causes this. In humans, this gene is known as C-SRC gene. (protooncogene)
viral SRC = oncogene

Question 2

What does the oncogenic version of C-SRC do?

Answer 2

Oncogenic version causes cells to become tranformed

Question 3

What are the characteristics of transformed cells into cancer cells?

Answer 3

They lose their contact inhibition
Have an altered shape
They are immortal
Dont need GFs
Tumorigenic
Anchored-independent growth
Increased glucose uptake

Question 4

What is Hras and what happens when it is mutated?

Answer 4

Hras - taype of Ras. It cannot hydolyse GTP to GDP, always bound to GTP so always active and that drives proliferation and division.

The mutation that happens in Hras that keeps it active is a point mutation. Glycine to a Valin in the aa sequence at the 12th point.

Question 5

What are the 3 types of Ras genes?

Answer 5

Hras
Kras
Nras

Question 6

What drug targets Kras and how ?

Answer 6

Amg510 is a drug that targets the mutated version of Kras

Binds to GDP bound Kras, which inhibits that Kras from binding to GTP

Used with chemo and now started using anti-PD1 a type of immunotherapy

Boosts expression of inflammation

Question 7

What are the downfalls that face drugs that attack Kras ?

Answer 7

Adaptive resistance, overtime becomes ineffective

This is because Kras can be amplified

Sometimes drug binding site is mutated so drug cannot bind

Sometimes its downstream signalling becomes more active will still work in spite of Kras

Question 8

What are the 3 different types of MYC?

Answer 8

CMYC
NMYC
LMYC

Question 9

What is MYC ?

Answer 9

It is in the nucleus and promotes growth. GFs

over 10 copies = tumour formation

Question 10

What are the 3 ways MYC can become oncogenic? Give examples of when they have happened

Answer 10

1. Gene amplification - elevated copy number of MYC e.g Neuroblastoma where NMYC becomes amplified
2. Chromosomal translocation - position of gene changes to a different chromosome where the gene promoter may be more active, so more MYC will be made e.g Burkitt lymphoma in the CMYC, gets transferred under an IGH promoter in an immunoglobular gene
3. Provirus integration - MYC under control of viral promoter (very active) e.g. AVL virus that causes leukaemia

Question 11

In RSV induced transformation, the genes responsible include

Answer 11

Gag
Pol
Env
X = SRC

Answer 12

Cancer mainly caused by mutagens
Mutation on protooncogenes causes oncogenes. This happens via mutations

Question 13

What is Hras and what happens when it is mutated?

Answer 13

Hras - type of Ras. It cannot hydrolyse GTP to GDP, always bound to GTP so always active and that drives proliferation and division.

The mutation that happens in Hras that keeps it active is a point mutation. Glycine to a Valin in the aa sequence at the 12th point.