Abstract 5285: COSMIC: comprehensively exploring oncogenomics
Authors: Forbes Simon A. , Bindal Nidhi , Beare David , Bamford Sally , Cole Charlotte G. , Ward Sari , Leung Kenric , Kok Chai Yin , Jia Mingming , De Tisham , Sondka Zbyslaw , Stratton Michael R. , Campbell Peter J. 
Published: July 2016

COSMIC (http://cancer.sanger.ac.uk) is an expert-curated database of somatic mutations causing human cancer. Broad and comprehensive in scope, its 75th release (Nov 2015) describes over 3.7 million coding mutations across all human cancer disease types. Mutations are annotated across the entire genome, but expert curation is focused on almost 200 key cancer genes. Now encompassing the majority of molecular mutation mechanisms in oncogenetics, COSMIC additionally describes 10 million non-coding mutations, 1 million copy number aberrations, 9 million gene expression variants and almost 8 million differentially methylated CpG’s. This information combines a consistent interpretation of the data from the major cancer genome consortia and cancer genome literature, with hand-curation of over 22,000 gene-specific literature publications.

With such a large volume of data, it is increasingly important to indicate which information is most significant. All mutations in COSMIC are now given a functional significance score, calculated using the FATHMM algorithm. In addition, a mutation can also be tagged as low-impact if they are described as a polymorphism in normal human genomes. All this information is available for selection and exploration in the COSMIC website (http://cancer.sanger.ac.uk), and for download via COSMIC Downloads (http://cancer.sanger.ac.uk/download). In addition to this broad database, the Cancer Gene Census (http://cancer.sanger.ac.uk/census) is a project within COSMIC aiming to identify and characterize all genes known to cause cancer, currently describing over 570 genes. This Census is now a priority focus of development, with a dedicated curator explicitly defining the range of genes driving cancer, including primary alleles and mechanisms and the diseases which are induced, with detailed supporting evidence.

In addition to these analytical websites, expert-curated lists and now a GA4GH Beacon, COSMIC also hosts a full Oncology Genome Browser (http://cancer.sanger.ac.uk/genome). This fully-featured system allows the exploration of all cancer somatic mutation data collected in COSMIC alongside genomic annotations including coding genes, ncRNAs, SNPs and regulatory features. All data is vertically integrated, allowing exploration of how these many genetic mechanisms might promote oncogenesis, and how similar activating/inactivating mechanisms correlate. Amongst many interesting examples, there is a clear cluster of structural rearrangements immediately upstream of the BRD4 epigenetic modifier gene, affecting a region of multiple transcription control elements, and a substantial accumulation of abnormally hypermethylated CpG islands in the HOXA gene cluster on chromosome 7 coinciding with a group of HOTAIR and HOTTIP miRNAs. With multiple filters and selections available, these visualizations will increasingly support the exploration of how a variety of mutation mechanisms may act together to cause specific cancer diseases.

Citation Format: Simon A. Forbes, Nidhi Bindal, David Beare, Sally Bamford, Charlotte G. Cole, Sari Ward, Kenric Leung, Chai Yin Kok, Mingming Jia, Tisham De, Zbyslaw Sondka, Michael R. Stratton, Peter J. Campbell. COSMIC: comprehensively exploring oncogenomics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5285.