Genetics & Cancer Flashcards
what type of mosaicism leads to cancer?
somatic mosaicism
- largely caused by post-zygotic mutations
what are cell characteristics for cancer?
- Proliferation
- Evade immune response
- Acquire a vascular supply
- Avoid apoptosis
- Metastasis
what genes are involved in cancer?
- oncogenes (switch on to make tumours survive)
- tumour suppressor (turn on to make tumour go down)
- DNA repair genes
- drug metabolism (genes that metabolise carcinogens)
what are driver mutations?
mutations that drive carcinogens
what are passenger mutations?
incidental mutations that happen because the tumour is unstable
what is methylation?
modification of histones (including de-acetylation) this represses transcription
= usually occurs on cytosine bases just before guanine bases
(about body switching genes off that doesn’t change sequence of cells themselves)
- allows environment to affect your genome
what is the clinical importance of methylation?
- Abnormalities of methylation cause genetic disease
- Methylation causes gene silencing in cancer
- Histone de-acetylation is a drug target
- A mechanism by which environment affects gene expression e.g. Starvation during pregnancy affects fetus
- Methylation makes mutation (C to T) more likely
why do tumours get so many mutations?
- Cancers develop genomic instability – the cells gain a high level of mutability.
- Loss of DNA repair and increased mutability is an essential characteristic that allows evolution of cancers
why do you have to keep changing treatments of cancers?
because cancers are highly mutable →you will end up with ball of cells and they all have lots of different mutations - so if you find pathway and treat it, you will kill one clone of cancer but there’s more different clones as well that won’t be killed so that’s why you have to keep changing treatment
what explains how cancer can be caused by inherited mutations or purely somatic phenomenon?
tumour suppressors & 2 hit hypothesis
what is knudsons two hit hypothesis?
the idea that you need 2 hits for cancer (hits = mutation)
if inherited mutation (1st hit) then more likely to get acquired mutation (2nd hit) and lead to cancer
if 1st hit is sporadically acquired mutation then much harder to get 2nd acquired mutation leading to cancer
what are mechanisms of gene activation?
- Duplication of the gene
- Activation of the gene promoter
- Change in amino acid sequence – active protein configuration
what is the BRAF V600E gene?
V600E is a driver genetic mutation in the BRAF gene
what is BRAF?
a gene that provides instructions for making a protein involved in transmitting signals within cells
Mutations in this gene can lead to uncontrolled cell growth and division, which is a hallmark of cancer
what is FISH?
the fluorescence technique that allows us to light up a very specific piece of chromosome
