Genetic Cancer Predisposition Flashcards
What is a germline mutation
Gene change reproductive cell (egg or sperm)
Becomes incorporated into DNA of every cell in body of offspring
What kind of cancer does germline mutation cause?
Cancer Syndrome
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
What is an oncogene?
Mutated proto-oncogene
What does an oncogene do
Promote cell division
Promote cell proliferation
Causes cancer
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?
Two mutations that disable 2 tumour suppressor 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?
DNA repair mechanisms
How many genes are invlved in DNA repair?
2
How does the failure of DNA damage response genes lead to cancer?
Both genes fail
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?
Doesn’t repair mutations
Worsens mutation
(e.g.instead of fixing mutated base it alters the complementary one to match)
What does a defective Mismatch repair gene lead to?
Micro satellite Instability (MSI)
Give an example of a dominant inherited cancer syndrome cause by an oncogene?
MEN2 (multiple endocrine neoplasia)
Caused by RET gene
Give an example of a dominatly inherited cancer syndrome caused by defective tumour supressor genes?
Breast/ovarian cancer 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 higher risk of cancers of digestive & gynaecological tracts
What DNA repair genes are defective in Lynch syndrome?
MLH1
MSH2
‘Other’
How else do genetics contribute to/cause cancer?
Autosomal Recessive Syndromes
Multiple modifier genes of lower genetic risk affect expression of more important genes
Whats the name for new mutations?
De novo mutations
Where do De Novo mutaions occur?
Parent germ cell
Why do inherited cancer susceptibility genes appear to skip generation?
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 history of CRC.
How does an adenoma become a carcinoma?
Normal epithelium gains APC mutation
Hyper proliferative 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 large intestine that can lead to colorectal cancer
What is HNPCC?
Hereditary Non-Polyposis Colorectal Cancer
Hereditary condition leading to colorectal cancer with no adenomas
What is the difference between genome & exome sequencing?
Genome sequencing - entire genome
Exome sequencing - only exon sequencing, no introns
What is Microsatellite Instability?
Condition caused by defective MMR genes
Genes are hypermutatable
Multiple mutated nucleotides form microsatellite fragments
