Genetic Cancer Predisposition Flashcards
What kind of cancer does germline mutation cause?
Cancer Syndrome or family cancer syndrome
what 3 types of genes are involved in pre-disposition to cancer?
Oncogenes
Tumour-supressor Genes
DNA damage-response genes
What is a proto-oncogene?
A normal gene that codes for proteins which regulate cell growth/differentiation
How does a proto-oncogene mutate?
To an oncogene
What is an oncogene?
The mutated form of a proto-oncogene
/What does an oncogene do
Oncogenes promote cell division, causing cancer when stuck in the “on” mode.
What do tumour supressor genes do?
Inhibit cell cycle & promote apoptosis
How many mutations are required to disable tumour supressor genes?
2, one for each “brake”
Explain the two-hit hypothesis?
The two mutations that disable the 2 tumour supressor genes leading to cancer.
1st mutation disables brake 1 (susceptible carrier)
2nd mutation disables 2nd brake (leads to canceR)
What is a cell called with one tumour supressor gene disabled?
A susceptible carrier
What are DNA damage response genes?
The repair mechanisms of DNA
How many genes are invlved in DNA repair?
2
How does the failure of DNA damage response genes lead to cancer?
When both genes fail the accumulation of mutations in other critical genes speeds up.
What is the MMR gene?
Mismatch repair gene.
What does a normal MMR gene do?
Repairs basic mutations
What does a defective MMR gene do?
It either doesnt repair the mutations or worsens them.
E.g. instead of fixing a mutated base it alters the complementary one to match.
What does a defective Mismatch repair gene lead to?
Microsatellite Instability. (MSI)
Give an example of a dominant inherited cancer syndrome cause by an oncogene?
MEN2 (multiple endocrine neoplasia) caused by the RET gene
Give an example of a dominatly inherited cancer syndrome caused by defective tumour supressor genes?
Breast/ovarian cancer are far more likely in people with defective BRCA1 or BRCA2 genes.
Example of cancer syndrome caused by defective DNA repair genes?
Lynch syndrome (HPNCC) gives people a much higher risk of cancers of digestive & gynaecologic tracts.
What DNA repair genes are defective in Lynch syndrome?
MLH1 & MSH2 amonst others.
How else do genetics contribute to/cause cancer?
- Autosomal Recessive Syndromes
- Multiple modifier genes of lower genetic risk affect how much more important genes are expressed.
Whats the fancy fucker name for new mutations?
De novo mutations
Where do De Novo mutaions occur?
In the parent germ cell
Why do inherited cancer susceptibility genes appear to skip generation?
Because they are mainly dominant with incomplete penetrance
What are specifc risk factors for Breast Cancer?
Age,
Early puberty,
Late menopause
using oestrogen
What are specific risk factors for Colorectal cancer(CRC)?
High-fat Low-Fibre diets
Inflammatory Bowel Disease
Family hisotry of CRC.
How does an adenoma become a carcinoma?
- > Normal epithelium gains APC mutation
- > Hyperproliferative epithelium has K ras mutation
- > Adenoma experieicnes p53 mutation
- > Carcinoma produced.
What does polyposis mean?
Formation of multiple Adenomas
What is FAP?
Familial Adenomatous Polyposis
Hereditary condition leading to formation of multiple adenomas in the large intestine that can lead to colorectal cancer.
What is HNPCC?
Hereditary Non-Polyposis Colorectal Cancer
A hereditary condition leading to colorectal cancer with no adenomas
What is the difference between genome & exome sequencing?
Exome sequencing only sequences the exons, ignoring the interons.
What is Microsatellite Instability?
A condition caused by defective MMR genes where yours genes are hypermutatable. multiple mutated nucleotides form microsatellite fragments
