Cancer-associated genes
19 February 2008
All cancers occur due to abnormalities in DNA sequence. The steady accumulation of these abnormalities throughout life ultimately means that one in three people in the Western world develops cancer. This year, the Cancer Genome Project - an international collaboration led by Professor Michael Stratton and colleagues at the Wellcome Trust Sanger Institute - has dramatically expanded the database of known cancer genes, adding significantly to our understanding of cancer biology and fuelling research into the development of new treatments.
The project set about probing the genetic make-up of cells taken from 210 different human cancers. The study focused on the genes encoding all 518 known human protein kinases, enzymes that regulate other proteins through the addition of a phosphate residue. These key molecular players can have a strong influence on cell growth and division and if not working properly can trigger tumour development.
The molecular scrutiny revealed over 1000 different mutations. However, the presence of a mutation does not necessarily mean that it is contributing to uncontrolled cell growth. Indeed, most changes appear to be ‘passenger’ mutations incidental to tumour development. But the researchers highlighted 158 mutations in 120 kinase genes as possible ‘drivers’ of disease.
Although it adds considerably to the 350 genes previously implicated in cancer, the study highlights how genetically complex even a single tumour is. And as each tumour type turned out to have a wide range of driver mutations, no obvious drug targets emerged for particular cancers. Nevertheless, the study has opened up a whole host of new molecular pathways to investigate and drug targets to explore.
Further reading
- Greenman C et al. Patterns of somatic mutation in human cancer genomes. Nature 2007;446(7132):153-8.