Genetic predesposition to cancer Flashcards
define cancer
genetic disease of somatic cells
Mutation that occur in nongermline tissues
Somatic - non-heritable
Germline mutations
Present in egg or sperm - heritable - cause cancer family syndromes
3 genetic processes associated with cancer
Oncogenes
TSG
DNA damage-response genes
Difference between:
Proto-oncogenes
Oncogenes
Proto-oncogenes - normal - codes for proteins to regulate cell growth and differentiation.
Oncogenes - can accelerate cell division - continuous = cancer
1 Hit hypothesis
1st mutation (leads to accelerated cell division) - oncogenes
2 Hit hypothesis
Cancer arises when both brakes fail - TSG
Mismatch repair failure
Microsatellite Instability (MSI) - phenotypic evidence that MMR is not functioning normally - micro satellite fragments (simple seq rpts)
MMR corrects - errors - single base mismatches or short insertions and deletions
De novo mutations
new mutation in germ cell - no fam history
Polyposis (multiple adenomas) types
FAP (Familial Adenomatous Polyposis,
AFAP (attenuated FAP)
MAP - recessive MYH associated polyposis
Gene - DNA repair by HR (homologous recombination)
BRAC2
main breast cancer - Main checkpoint gene
BRAC1
retinoblastoma - germ line or somatic mutation?
germ line mutation in RB1 gene
What mutations advances adenoma to carcinoma?
p53
Which polyposis is this?
Adenoma, high penetrance, extracolonic tumour, CHRPE ~ present, (untreated polyposis - 100% cancer)
FAP
