By Mark Gould, London
Scientists working on the cancer genome project announced this week that they have made an “unexpectedly early” discovery of the mutant gene responsible for 70% of all malignant melanomas. The project, which is funded by the Wellcome Trust, is based at the Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire.
The researchers predict that the finding, which occurs in the early stages of a project involving 50 million experiments, will mean that the “vast majority” of the genes involved in the most common cancers will be identified within the next five years. The discovery is set to revolutionise cancer treatment, with the ability to target specific molecular abnormalities, they say.
The incidence of melanoma, which kills 1600 people a year in the United Kingdom and some 7400 in the United States, has doubled over the past decade. It is responsible for 11% of all skin cancers but almost all of the deaths from skin cancer because of its ability to metastasise rapidly.
The researchers, writing in the online version of Nature (www.nature.com), say that the mutation in the gene known as BRAF is “so clear cut” that they are five years away from offering drugs to block its action.
Scientists on the project began work in February 2001 to identify which of the 30000 human genes are involved in cancer. Professor Mike Stratton, one of the leaders of the project, said that the BRAF mutation was one of the first 20 they looked at.
“Because mutated BRAF is permanently `on,’ we have already started searching for drugs that will switch it back off,” Professor Stratton said. He said that slow computers were hampering progress to identify all the genetic components of all cancers.
But Professor Stratton said the consensus was that not all cancers shared one common genetic mutation. Project co-leader Dr Andy Futreal said that 1000 different human cancer samples, representing 43 different types of cancer, had been studied and that the initial results were “quite striking.”
“Amongst the 2200 odd letters that go to encode the BRAF protein, one of those accounted for about 80% of all the mutations found. A single change, from a T to an A, in the spelling of the BRAF sequence will account for the mutation. It’s extraordinarily specific.”
The T to A switch in BRAF is also found in ABL, a gene found in myeloid leukaemia. This has been successfully treated with the new generation of tyrosine kinase inhibitors, such as imatinib (Glivec). The Wellcome Trust has now patented the gene to facilitate research on new treatments.
Source: BMJ 2002;324:1412 ( 15 June )