Molecular hallmarks of cancer cells Flashcards
What are caretaker genes?
Maintain genetic stability by repairing damaged DNA and replication errors. I.e. tumour suppressor genes when active
What is a common feature of most tumour cells?
Genetic instability
What are driver mutations?
Mutations in proto-oncogenes/tumour-suppressor genes that drive cancinogenesis.
What are the two different types of tumour suppressor gene?
Gatekeepers and caretakers
What are gatekeeper genes?
Play important roles in regulating normal growth:
- negative regulators of the cell cycle and proliferation
- positive regulators of apoptosis
- positive regulators of cell differentiation
What are caretaker genes?
Maintain genetic stability
- DNA repair genes
- controlling accuracy of mitosis
What sort of mutations are required of tumour suppressor genes for carcinogenics?
Loss of function - point mutations, deletions/insertions, chromosomal rearrangements, epigenetic silencing
Do loss of function mutations contribute directly to the tumourigenic phenotype?
No - such mutations simply create the conditions whereby mutations have a chance to arise in gatekeeper TSGs.
What kind of mutation usually provides the first hit for a TSG?
Point mutation in the coding sequence.
What kind(s) of mutation provide the second hit for a TSG and why?
Chromosomal non-disjunction
Gene conversion
Mitotic recombination
Epigenetic inactivation through promotor methylation
These types of mutational events are 3x more common than point mutations.
Which gene is involved in retinoblastoma?
Gene: RB1
Tumour: retinoblastoma
What gene and principle tumours are involved in Li-Fraumeni?
Gene: p53
Tumour: sarcomas, breast
What gene and principle tumour is involved in familial adenomatous polyposis?
Gene: APC
Tumour: colorectal
What genes and principle tumours are involved in familial breast cancer?
Genes: BRCA1, BRCA2
Tumours: breast, ovarian
What genes and principle tumours are involved in HNPCC?
Genes: hMLH1, hMSH2
Tumours: colon, endometrial