6. Tumour Suppressor Genes (Retinoblastoma and the two hit hypothesis, p53)

Описание: Cancers occur as a result of damage (in the form of mutations) to a cells DNA that results in the formation of malfunctioning proteins. The mutated proteins give the cancerous cells a number of specific traits, outlined in the 'hallmarks of cancer' (   • 4. Hallmarks of Cancer (part 1)  ).

The genes that are mutated in cancers can be divided into two groups - tumour suppressor genes and proto-oncogenes.

Tumour suppressor genes are genes that produce proteins that are involved in stopping mutated cells from dividing, and also act as the brakes on the cell cycle at its various checkpoints.

The retinoblastoma gene is a gene that is involved in stopping cells from crossing the G1 checkpoint in the cell cycle, preventing cells from entering S phase and replicating their DNA in preparation for cell division.

For the retinoblastoma gene to be rendered inactive, it needs a mutation in both of its copies (alleles). This is explained by the 'two hit hypothesis'.

P53 is another example of a significant tumour suppressor gene. It is active during the cell cycle, acting by halting damaged cells at the checkpoints and then ordering the cell to destroy itself by the process of apoptosis.