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GEN News Highlights : Mar 8, 2007

More Mutations than Previously Thought Are Implicated in Cancer

Challenge lies in differentiating between the driver mutations that cause cancer and the harmless passenger mutations.

The number of mutated genes that drive development of cancer is greater than previously thought, according to a survey of the human genome in the disease done at the Wellcome Trust Sanger Institute.

The scientists sequenced more than 250 million letters of DNA code, covering more than 500 genes and 200 cancers. The team studied more than 500 kinases, some of which have been previously implicated in causing cancers. For example, study of the BRAF gene was expanded to include breast, lung, colorectal, and stomach cancers.

The new research showed that mutations in cancers can be divided into drivers or passengers. Driver mutations are the ones that cause cancer cells to grow, and   each cell type carries passenger mutations that make no contribution to disease development. The challenge for biologists will be to distinguish the drivers from the larger number of passengers.

The team identified possible driver mutations in 120 genes, most of which had not been seen before. "The human genome is a vast place and this, our first deep systematic exploration in cancer, has thrown up many surprises,” comments Mike Stratton, co-leader of the Cancer Genome Project at the Sanger Institute. "We have found a much larger number of mutated driver genes produced by a wider range of forces than we expected."

Andy Futreal, also co-leader of the Cancer Genome Project points out that  “this suggests that many more genes contribute to cancer development than was thought."

The team also found that the mutations carry coded messages within them. The type of mutation found varies markedly between individual cancers, reflecting the processes that generated the mutations, some of which were active decades before the cancer showed itself. Some of these patterns can be deciphered, such as the signatures of damage from ultraviolet radiation or cancer-causing chemicals in tobacco.