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
Which polyposis is this? Late onset, no CHRPE, few colonic adenomas
AFAP (attenuated FAP)
Which polyposis is this? Similar GI feature to AFAP, mut in MYH gene
MAP (recessive MYH associated polyposis)
