Cancer genetics Flashcards
What can cause cancers?
Somatic mutations
(e.g. protoncogene, DNA repair gene, tumour suppressor gene)
Inherited germ line mutations
Is cancer monogenic?
Almost never, cancer appears though the accumulation of many mutations
What do protooncogenes do?
On switch, cause cell to grow and divide (tightly controlled)
How do oncogenes cause cancer?
Gain of function mutation in protooncogene
Unresponsive to control/permanently switched on
Uncontrolled cell growth and division (neoplasia)
What do tumour suppressor genes do?
Off switch
Arrest cell cycle in case of DNA damage, or incorrect progression of previous phase
How do TSG mutations cause cancer?
Cells continually divide when damaged DNA
How can cancer be caused by loss of activity (gene inactivated) (3 ways)?
In TSG/ DNA repair gene
Loss of function mutation Gene silencing (hypermethylation) Loss of chromosome (e.g. non disjunctinon)
How many mutations of an oncogene do you need to get cancer?
1
How many mutations of TSG do you need to get cancer?
2
Why can sometimes one somatic mutation lead to cancer from TSG?
One mutation inherited in the germline
Thus only one somatic mutation needed
What does Knudson’s two hit hypothesis suggest?
Individuals with an inherited cancer causing mutation are far more likely to get the cancer (younger and more sites)
Most tumour suppressor genes require both alleles to be inactivated,
Why is somatic mutation dectetion for cancer beneficial?
Enable classification of tumour prognosis and treatment so Less treatment for those with good prognosis
May mean target therapy
Which genes predispose to familial breast cancer?
BRCA1/2 and p53
What do BRCA genes do?
Repair DNA double strand breaks
How is familial breast cancer inherited?
Autosomal dominant
