Researchers have discovered the one in 10bn genetic mutation that causes the death of hundreds of British victims of the harshest form of skin cancer, malignant melanoma.
The discovery is the first success for the world's most ambitious effort to decode the genetic alterations that lead to cancer, the cancer genome project, based at the Wellcome Trust Sanger Institute near Cambridge.
Work has begun on a drug to halt the effects of the mutation. The researchers, whose work is published in the online version of the journal Nature this week, say clinical trials could begin in five years.
Melanoma affects about 6,000 Britons each year, killing more than a quarter of them. The Sanger Institute team found that in 70% of melanoma tumours, there are mutations in a single gene, Braf, which governs cell growth. Some 80% of these mutations involve a change in just one of the 3bn-plus "letters" that make up the human genetic code, or genome. The "letter" changes from "T" to "A", one of three possible variations - in other words, a one in 10bn alteration that leads to disaster.
All cancers are genetic in origin, because tumours cannot grow until a series of genetic safety catches are flipped to "off" and a series of genetic switches are flipped to "on". But that does not mean they are inherited. The genes can be switched on and off by environmental factors and by copying errors made naturally when cells divide.
"The most exciting thing about this discovery is that it could be a direct lead to new treatments for malignant melanoma," said Professor Mike Stratton, who is head of the cancer genome project.
"Because mutated Braf is permanently stuck in the 'on' position, we have already started searching for drugs that will switch it back off. These drugs would be expected to stop the growth of these cancers."
Braf is the gene coding for one of a chain of chemical signals that instruct cells to divide. The mutations cause it to be on when it should be off.
Project scientists are optimistic about a Braf-targeted drug because the target is similar to that of an existing drug, Glivec, which has been effective in treating another cancer, chronic myeloid leukaemia (controversially, the expensive drug has not been approved for full National Health Service use).
Melanoma accounts for only 11% of skin cancers but almost all the deaths from skin cancer - 1,600 a year in Britain. Four out of five cases are caused by excessive exposure to the sun. Other risk factors are fair skin, large numbers of moles (50 to 100) on the body, and age - the 40 to 60 age group is most affected. The incidence of melanoma is increasing more rapidly in men than in women. If untreated the cancer cells can spread to other parts of the body, such as the brain, lung or liver.
The cancer genome project is an offshoot of the human genome project, which tabulated the entire sequence of "letters" making up the 30,000-gene template for the human organism. Prof Stratton's team have compiled the world's largest collection of cancer cell lines - about 1,500 in total - and are comparing the genes in them with the genes in the human genome project data, searching for what makes cancer cells genetically different.
