8. Causes of cancer, TSGs and Oncogenes Flashcards
What is meant by the term tumour suppressor gene?
the normal function of these genes is inhibition of cell proliferation or repair of damaged DNA – abnormalities (of both alleles) of tumour suppressor genes can drive a normal cell towards a cancerous state
What is meant by the term oncogenes?
the normal function of these genes is an increase in cell proliferation – abnormalities of only one allele of an oncogene can drive a normal cell towards a cancerous state
What are the risk factors for cancer?
Old age
Environment
Genetic predisposition
What is the loss of function of a tumour supressor gene product as a consequence of?
Less of the gene product being expressed
Or a mutation in the gene such that the resultant protein has reduced or a loss of function
What is the Knudson “two hit hypothesis”
Requires the loss of both copies of the tumour suppressor gene
What are example of TSGs
p53 gene
APC gene
Rb gene
What is the assocaited inherited cancer syndrome for the Rb tumour suppressor gene?
Retinoblastoma
What is the assocaited inherited cancer syndrome for the APC tumour suppressor gene?
FAP
What is the assocaited inherited cancer syndrome for the MSH2/MLH1 tumour suppressor gene?
HNPCC (lynch syndrome)
What is the assocaited inherited cancer syndrome for the BRCA1/BRCA2 tumour suppressor gene?
Breast cancer and ovarian cancer
What is the assocaited inherited cancer syndrome for the p53 tumour suppressor gene?
Li-Fraumeni syndrome
What is the sporadic form of the knudson hypothesis?
a mutation has to occur in both copies of the retinoblastoma gene, unlikely
the longer the period of time that elapses the more likely this is, but it is unlikely to occur more than in one cells. Hence tumours occur late and are unilateral.
What is the familial form of the knudson hypothesis?
the child inherits from one mutant copy of the retinoblastoma gene, so only one additional mutation needed
the disease occurs earlier and also there is a high probability of it occurring in more than one cell, and thus tumours may be multi-focal and bilateral.
What are the features of p53?
Altered in more than 50% of human cancers
Involves in a pathway that responds
What are the features of p53?
Altered in more than 50% of human cancers
Involves in a pathway that responds to DNA damage and allows repair or apoptotic cell death
It is a transcription factor: regulates other genes
What are the clinical features Li-Fraumeni syndrome?
Cancer at a young age
Development of adrenocortical carcinoma Development of soft-tissue sarcomas Acute leukaemias and brain tumours Osteosarcomas Premenopausal breast cancer is common
What is the BRCA1 tumour supressor gene?
Isolated by positional cloning as one of the genes predisposing to early onset breast and ovarian c
What is an oncogene?
Involved in cancer by an increased activity of the (proto)oncogene stimulating an increase in cell number
When the does an oncogene gain its fucntion?
When more of the gene product being expressed
Mutation in the gene such that the resultant protein has increased function
Expression ocurring in the wrong cell type/ wrong time
What will gaining an oncogene result in?
Leads to a stimulation of a critical cell process
