Analysis of gene mutations that drive cancer

10 March 2007

A new analysis of cancer genomes has revealed the presence of substantially more mutations than previously suspected. In a recently published paper in Nature, a Cancer Genome Project team led by researchers from the UK Wellcome Trust Sanger Institute sequenced the genomes from more than 200 different human cancer cells. Cancer is known to arise via the accumulation of certain types of genetic mutation in dividing cells that together disrupt normal regulation of cellular function and growth, and lead to uncontrolled proliferation. These cancer-associated mutations are sometimes referred to as ‘driver’ mutations (for example, in genes involved in DNA proofreading and repair functions, or in cellular replication checkpoints); however, cancer cell genomes also include other mutations not specifically associated with carcinogenesis, dubbed ‘passenger’ mutations.

The Sanger team presents an analysis of more than 1000 mutations identified in the coding portions of over 500 protein kinase genes, a class frequently associated with cancer [Greenman C et al. (2007) Nature 446(7132):153-8] . They found that the majority of mutations were likely to be passenger mutations, but nevertheless identified potential driver mutations in more than 120 genes. Cancer Genome Project co-leader Dr Andy Futreal commented that "…buried amongst [passenger mutations] are much larger numbers of driver mutations than was previously anticipated. This suggests that many more genes contribute to cancer development than was thought" (see press release). The authors propose that the full repertoire of cancer mutations will not become apparent until thousands of cancer cell genomes have been systematically analysed.

Comment: This paper is an early publication from a very large cancer genome project, and reveals something of the range and complexity of cancer mutations that exist. As well as providing important new information about patterns of mutation in different forms of cancer and distinguishing features of passenger and driver mutations, it also identifies a wealth of novel cancer-associated driver mutations. These may prove extremely valuable in understanding the genetic and pathological processes that underlie cancer, and in the search for new drugs and other therapeutic approaches to combat the disease.

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