Abstract 5142: COSMIC: Exploring the world's knowledge of somatic mutations in cancer.
Authors: Leung Kenric , Kok Chai Yin , Shepherd Rebecca , Gamble John , Jia Mingming , Bamford Sally , Ward Sari , Cole Charlotte , Beare David , Bindal Nidhi , Gunasekaran Prasad , Teague Jon , Forbes Simon A. , Stratton Michael R. , Campbell Peter 
Published: August 2014

COSMIC, the Catalogue Of Somatic Mutations in Cancer (http://cancer.sanger.ac.uk/), is the world's largest database of curated somatic mutations. The current version (v62, Nov 2012) has over a million mutations across 800000 samples from 15327 peer-reviewd publications, online data portals such as TCGA, ICGC, the IARC p53 database and the Cancer Genome Project (CGP) at the Sanger Institute, UK. The project aims to build a comprehensive catalogue of somatic mutations prioritized by the Cancer Gene Census (http://cancer.sanger.ac.uk/cancergenome/projects/census/), allowing users to explore correlations between cancer phenotypes and mutant genotypes. At present, a full distribution of somatic mutations have been curated across 116 known cancer genes and 169 gene fusion pairs. A focus on cancer genomes has recently emerged from the rapid expansion of whole genome/exome resequencing, as shown by our "COSMIC Genomes" website (http://cancer.sanger.ac.uk/cancergenome/projects/studies/), already comprising over 4500 tumours across a variety of cancer types.

There are a number of ways to examine the data within COSMIC. A newly released website provides an intuitive interface for users to scrutinize the data through numerous filters, including mutation types, histology and tissue types. This is supplimented with statistical summaries presented in many graphs and charts. The website includes a COSMIC genome browser for views across combined cancer genomes, including all mutation types in one graphical window. Many other resources are designed for bioinformatic access including a Biomart, and FTP downloads in a variety of formats (ftp://ftp.sanger.ac.uk/pub/CGP/cosmic/). We actively seek to integrate with the wider bioinformatics community and are integrated within the UCSC and Ensembl genome browsers.

COSMIC both documents mutation trends in known cancer genes, and combines distributed information to allow substantial mining of these data for discovery of novel correlations. COSMIC can aid discovery of novel recurrence patterns between variants, genes and tissues in different mutant genotypes and cancer phenotypes. The most frequently mutated gene in COSMIC (v62, Nov 2012), is JAK2 with the p.V617F mutation observed in 36% of all blood cancers examined. This is followed by TP53 with a variety of truncating mutations observed at a total frequency of 29.7%, and KRAS, found mutated in 21% of cancers, most frequently p.G12D in pancreatic tumours. Focusing particularly on the 4571 whole genomes, the most mutated gene is unsurprisingly TP53 at 27.57% (followed by TTN, MUC16, PIK3CA, CSMD3). Many techniques may identify putative novel cancer genes outside the cancer gene census. For instance, in Lung cancer the most mutated genes (correcting for CDS length) are TPTE, FAM5C, CDH10 and KEAP1. The rapid combination of increasingly large datasets in COSMIC ensure its future relevance in discovery of new trends in cancer genetics.

Citation Format: Kenric Leung, Chai Yin Kok, Rebecca Shepherd, John Gamble, Mingming Jia, Sally Bamford, Sari Ward, Charlotte Cole, David Beare, Nidhi Bindal, Prasad Gunasekaran, Jon Teague, Simon A. Forbes, Michael R. Stratton, Peter Campbell. COSMIC: Exploring the world's knowledge of somatic mutations in cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5142. doi:10.1158/1538-7445.AM2013-5142