International network of cancer genome projects

The genomes of all cancers accumulate somatic mutations. These include nucleotide substitutions, small insertions and deletions, chromosomal rearrangements and copy number changes that can affect protein-coding or regulatory components of genes. In addition, cancer genomes usually acquire somatic epigenetic ‘marks’ compared to non-neoplastic tissues from the same organ, notably changes in the methylation status of cytosines at CpG dinucleotides. A subset of the somatic mutations in cancer cells confers oncogenic properties such as growth advantage, tissue invasion and metastasis, angiogenesis, and evasion of apoptosis. These are termed ‘driver’ mutations. The identification of driver mutations will provide insights into cancer biology and highlight new drug targets and diagnostic tests. Knowledge of cancer mutations has already led to the development of specific therapies, such as trastuzumab for HER2 (also known as NEU or ERBB2)-positive breast cancers and imatinib, which targets BCR-ABL tyrosine kinase for the treatment of chronic myeloid leukaemia. The remaining somatic mutations in cancer genomes that do not contribute to cancer development are called ‘passengers’. These mutations provide insights into the DNA damage and repair processes that have been operative during cancer development, including exogenous environmental exposures. In most cancer genomes, it is anticipated that passenger mutations, as well as germline variants not yet catalogued in polymorphism databases, will substantially outnumber drivers. Large-scale analyses of genes in tumours have shown that the mutation load in cancer is abundant and heterogeneous. Preliminary surveys of cancer genomes have already demonstrated their relevance in identifying new cancer genes that constitute potential therapeutic targets for several types of cancer, including PIK3CA, BRAF, NF1 (ref. 10), KDR, PIK3R1 (ref. 9), and histone methyltransferases and demethylases. These projects have also yielded correlations between cancer mutations and prognosis, such as IDH1 and IDH2 mutations in several types of gliomas. Advances in massively parallel sequencing technology have enabled sequencing of entire cancer genomes. Following the launch of comprehensive cancer genome projects in the United Kingdom (Cancer Genome Project) and the United States (The Cancer Genome Atlas), cancer genome scientists and funding agencies met in Toronto (Canada) in October 2007 to discuss the opportunity to launch an international consortium. Key reasons for its formation were: (1) the scope is huge; (2) independent cancer genome initiatives could lead to duplication of effort or incomplete studies; (3) lack of standardization across studies could diminish the opportunities to merge and compare data sets; (4) the spectrum of many cancers is known to vary across the world; and (5) an international consortium will accelerate the dissemination of data sets and analytical methods into the user community. Working groups were created to develop strategies and policies that would form the basis for participation in the ICGC. The goals of the consortium (Box 1) were released in April 2008 (http://www.icgc.org/files/ICGC_April_29_2008.pdf). Since then, working groups and initial member projects have further refined the policies and plans for international collaboration. Erratum in Nature. 2010 Jun 17;465(7300):966. Himmelbaue, Heinz [corrected to Himmelbauer, Heinz]; Gardiner, Brooke A [corrected to Gardiner, Brooke B]; Cross, Anthony [corrected to Cros, Anthony].