Question: are you close to finding the mutation that causes skin cancer?

Ken Dutton-Regester answered on 12 Mar 2012:

The simple answer is ‘yes’ and ‘no’.

For skin cancer, it develops through the gradual accumulation of mutations in a variety of genes that controls normal healthy cell functions. It has been estimated that for a normal skin cell (melanocyte) to develop into a cancer (or melanoma), it requires anywhere from 3 to about 15 mutations in key genes (this is a question that hasn’t been conclusively answered and is likely to be different for different people and tumours- a mutation in one gene may be more important than a mutation in another for example).

During my PhD (or the 3 years I have been working on melanoma), I have already found a number of mutations in genes that cause melanoma. Probably the biggest discovery so far that I have been involved in is finding 2 genes, called MAP3K5 and MAP3K9, which are mutated in about 25% of melanomas. These genes seem to be involved in a really funky, yet important biological function called ‘apoptosis’. Apoptosis is basically a suicide mechanism that normal cells can use if they realise they have got too many mutations occurring in their DNA, of which, they can no longer repair. In this sense, these cells can go into ‘apoptosis’ and kill themselves off so that cancer doesn’t develop (cool, huh). Mutations in MAP3K5 and MAP3K9 appear to interfere with the cells apoptosis function, allowing these cells to essentially live longer and cause melanoma.

Note that these mutations in MAP3K5 and MAP3K9 only occur in ~25% of patients; other genes we know are involved in melanoma are mutated from anywhere between 5%-60% of patients. As such, there is still a lot of variation between which genes are mutated in people and what the ultimate biological effect that these mutations have. Although within the last year (because of the cool sequencing technology), researchers probably found another ~15 genes involved in melanoma- there are probably heaps more to be found before we can fully understand the full picture of how melanoma develops.