Cancer genes: Drivers unwanted 14/3/07. By Giles Newton The Cancer Genome Project has found mutations in 120 kinase genes that appear to 'drive' cancer.

Cancers are caused by DNA mutations that give cells a growth advantage. Mutations in more than 350 genes have already been linked to cancers, but researchers suspect that there may be many more; by identifying the genes involved, they hope to understand how cancers begin and develop, and highlight targets for new anticancer drugs.

The Cancer Genome Project – an international study led by Michael Stratton and colleagues at the Wellcome Trust Sanger Institute – has now looked for mutations in all 518 known human kinase genes in 210 samples of cancer.

Kinases regulate the activity of many pathways involved in cell growth and division, and defects in some kinase genes have already been linked to cancers. They are also attractive targets for drug therapies; for example, the drug imatinib (Gleevec) has proved highly successful in treating chronic myeloid leukaemia, by inhibiting the kinase BCR-ABL.

By systematically sequencing all 518 kinase genes in the 210 samples, more than 1000 mutations were found. After sifting out 'passenger' mutations that do not contribute to cancer development, the team found 158 mutations in 120 kinase genes that appeared to be 'driving' cancer. Many of these genes had not been linked to cancer previously.

As they only looked at 518 genes in limited numbers of each cancer type, the researchers suggest that the repertoire of mutated human cancer genes is larger than anticipated.

The study was funded by the Wellcome Trust and the US National Institutes of Health.

Further reading

Greenman C et al. Patterns of somatic mutation in human cancer genomes. Nature 2007;446(7132):153–8.

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