genetics 2: tumour suppressor genes Flashcards
what do tumour suppressor genes do?
- regulate proliferation
- maintain integrity
- regulate cell death
- act as transcription factors, dna repair proteins / cell adhesion molecules
- usually inhibitory
what is Knudson’s two hit hypothesis?
sporadic cancer requires mutations in both copies of tumour suppressor genes
- hereditary cancer likely means one inherited gene is already mutated
what are the features of inherited cancer susceptibility?
- family history of related cancers
- unusually early age of onset
- bilateral tumours in paired organs
- synchronous or successive tumours
- tumours in different organ systems in the same individual
- mutation inherited through the germline
what is retinoblastoma?
sporadic malignant cancer of developing retinal cells
what mutation causes retinoblastoma?
RB1 tumour suppressor gene on chromosome 13q14
- RB1 encodes a nuclear protein that is involved in the regulation of the cell cycle
why are proto-oncogene mutations rarely hereditary?
you’d be a ball of cancer
- TS gene mutations can be passed on because both need to be damaged before disease develops
what are the functional classes of tumour suppressor genes?
- regulate cell proliferation
- maintain cellular integrity
- regulate cell growth
- regulate the cell cycle
- nuclear transcription factors
- dna repair proteins
- cell adhesion molecules
- cell death regulators -> suppress neoplastic phenotype
what are some examples of tumour suppressor genes and the cancers associated?
p53 (cell cycle regulator) -> many
BRCA1 (cell cycle regulator) -> breast, ovarian, prostate
PTEN (tyrosine and lipid phosphotase) -> prostate, glioblastoma
APC (cell signalling) -> colon p16-ink4a (cell cycle regulator) -> colon
MLH1 (mismatch repair) -> colon, gastric
what is p53?
‘guardian of the genome’
- tumour suppressor gene that only requires mutation of a single copy to cause dysregulation of activity
