Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA ©2007 Nature Publishing Group Correspondence and requests for materials should be addressed to P. A.F. (paf@sanger.ac.uk) or M.R.S. (mrs@sanger.ac.uk).. Supplementary Information is linked to the online version of the paper at www.nature.com/nature.Reprints and permissions information is available at www.nature.com/reprints.The authors declare no competing financial interests. Europe PMC Funders GroupAuthor Manuscript Nature. Author manuscript; available in PMC 2009 July 20. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.Cancers are clonal proliferations that arise owing to mutations that confer selective growth advantage on cells. The mutated genes that are causally implicated in cancer development are known as 'cancer genes' and more than 350 have thus far been identified (ref. 1 and http://www.sanger.ac.uk/genetics/CGP/Census/). Cancer genes have been identified by several different physical and genetic mapping strategies, by biological assays and as plausible biological candidates. Each of these approaches has identified a subset of cancer genes, leaving the possibility that others have been overlooked. The provision of the human genome sequence, therefore, led to the proposal that systematic resequencing of cancer genomes could reveal the full compendium of mutations in individual cancers and hence identify many of the remaining cancer genes2.Somatic mutations occur in the genomes of all dividing cells, both normal and neoplastic. They may occur as a result of misincorporation during DNA replication or through exposure to exogenous or endogenous mutagens. Cancer genomes carry two biological classes of somatic mutation arising from these various processes. 'Driver' mutations confer growth advantage on the cell in which they occur, are causally implicated in cancer development and have therefore been positively selected. By definition, these mutations are in 'cancer genes'. Conversely, 'passenger' mutations have not been subject to selection. They were present in the cell that wa...

Reactome (http://www.reactome.org) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we developed a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepresentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice.