Genome discovery set to revolutionise cancer treatments

Scientists have identified the genetic faults responsible for most lethal skin cancers in a ground-breaking study that could revolutionise the investigation of all kinds of tumours.

Mutations in a gene during the life of a patient cause normal skin cells to turn malignant, according to researchers attempting to screen the entire human genome for cancer genes.

The findings relating to the skin cancer gene are described as so clear cut that already the scientists are designing specific drugs to bring about a cure.

The scientists, working at the Wellcome Trust Sanger Institute in Cambridge, said the mutated gene, called BRAF, is found in 70 per cent of malignant melanomas – the most lethal form of skin cancer – and 10 per cent of colon cancers.

Unlike many previous "cancer gene" discoveries which have identified inherited predispositions to cancer, this latest study explains how the genetic material of a healthy cell becomes corrupted and turns into a tumour.

Professor Mike Stratton, one of the leaders of the Cancer Genome Project at the Sanger Institute, said the work showed how a mutation can cause a healthy cell to divide uncontrollably by flicking on its "growth switch" permanently.

"The most exciting thing about this discovery is that it could be a direct lead to new treatments for malignant melanomas," he said. "Because mutated BRAF is permanently stuck in the 'on' position, we have already started searching for drugs that will switch it back off."

A drug called Glivec has already shown promise against mutations in a similar gene called ABL, which causes chronic myeloid leukaemia. A drug against BRAF mutations would however take up to 15 years to develop, Professor Stratton said.

The findings, published yesterday in the online edition of Nature, resulted from a systematic sweep of the first 300 of the 30,000 or so genes decoded as part of the Human Genome Project.

Each gene will be analysed for cancer-causing properties and matched against cells taken from 48 different tumours, from breast and ovarian cancers to cancers of the prostate and lung.

Richard Wooster, one of the team leaders, said the £36m Cancer Genome Project will involve some 50 million experiments over five years. The BRAF gene was found among the first 20 genes that the scientists analysed and a change in just one of the "letters" of the gene's DNA code accounted for 80 per cent of the mutations.

Andy Futreal, another member of the Sanger team, said: "It was quite striking because it makes the changes in the BRAF gene the single most common mutation in malignant melanoma."

Although malignant mela-noma accounts for only 11 per cent of all skin cancers, it is responsible for nearly all the deaths from the disease. Last year, skin cancer killed more than 1,600 people in the UK alone – a death rate that is increasingly rapidly, especially among men.

"We know that all cancers are a disease of DNA," Dr Futreal said.

"With the human DNA sequence now available to us, we have started the lengthy and daunting task of trawling through the vast tracts of the genome to see if we can find the abnormal genes that drive cells to behave as cancers."

Professor Stratton said the discovery came after only 1 per cent of the genome had been screened and other major finds were sure to follow. "It shows that the hard wiring of cancer is in the DNA," he said.