Genetics & Cancer

Question 1

what type of mosaicism leads to cancer?

Answer 1

somatic mosaicism
- largely caused by post-zygotic mutations

Question 2

what are cell characteristics for cancer?

Answer 2

• Proliferation
• Evade immune response
• Acquire a vascular supply
• Avoid apoptosis
• Metastasis

Question 3

what genes are involved in cancer?

Answer 3

• 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)

Question 4

what are driver mutations?

Answer 4

mutations that drive carcinogens

Question 5

what are passenger mutations?

Answer 5

incidental mutations that happen because the tumour is unstable

Question 6

what is methylation?

Answer 6

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

Question 7

what is the clinical importance of methylation?

Answer 7

• 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

Question 7

why do tumours get so many mutations?

Answer 7

• 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

Question 8

why do you have to keep changing treatments of cancers?

Answer 8

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

Question 9

what explains how cancer can be caused by inherited mutations or purely somatic phenomenon?

Answer 9

tumour suppressors & 2 hit hypothesis

Question 10

what is knudsons two hit hypothesis?

Answer 10

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

Question 11

what are mechanisms of gene activation?

Answer 11

• Duplication of the gene
• Activation of the gene promoter
• Change in amino acid sequence – active protein configuration

Question 12

what is the BRAF V600E gene?

Answer 12

V600E is a driver genetic mutation in the BRAF gene

Question 13

what is BRAF?

Answer 13

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

Question 14

what is FISH?

Answer 14

the fluorescence technique that allows us to light up a very specific piece of chromosome

Question 15

how can cancers be analysed?

Answer 15

by genetic sequence (Molecular pathology) as well as by looking at them under a microscope

Question 16

is the predisposition to cancer monogenic or multifactorial?

Answer 16

it can be monogenic or multi-factorial

Question 17

what does MLH1 positive bowel cancer mean?

Answer 17

MLH1 protein is present and functional

Question 18

what does MLh1 negative bowel cancer mean?

Answer 18

indicates a loss or inactivation of the MLH1 gene in the tumor cells. MLH1 is one of the genes associated with DNA mismatch repair (MMR), and mutations or inactivation of this gene can lead to a failure in the MMR system