The COSMIC Cancer Gene Census - a comprehensive study of all mutated cancer-driving genes

The COSMIC Cancer Gene Census (https://cancer.sanger.ac.uk/census) is a catalogue of genes that drive all forms of human cancer. Since 2004, a consistent curation approach to the scientific literature has grown this resource into a comprehensive description of 723 genes, detailing how each gene contributes to disease causation The entire Cancer Gene Census has been fully re-evaluated, and each gene has been classified as Oncogene, Tumour Suppressor and/or Fusion gene - depending on their somatic mutation profile and functional role in carcinogenesis. Genes included in the CGC are characterised by the presence of somatic or germline mutations, which change the activity or expression of the protein product in a way that promotes one or multiple hallmarks of cancer. The minimum level of evidence required for CGC inclusion are at least 2 publications from independent research groups showing increased mutation frequency in at least one type of cancer; and 2 or more published experimental evidence of functional involvement of a gene in promoting the hallmarks of cancer. The functional description of how each mutated gene causes cancer is now underway, with approximately half the Census now described in both functional and mechanistic terms. These characteristics clearly show that many genes can participate in oncogenesis in multiple ways that are highly dependent on the type of genetic alteration and tissue in which the gene is expressed, as well as disease stage. Alongside this evidence-based characterisation of genes we know drive cancer, a “second tier” of genes is now encompassed in the Census, to describe genes implicated in oncology, but with less robust published evidence. These genes, often revealed by combining whole-tumour-genome sequencing studies are increasing rapidly in number and often underpin exciting new targets in oncology. Inclusion of these in the Census completes its ability to describe the contribution of inherited and acquired genetics to human oncology. With substantial research ongoing, the Census is updated with additional content every three months, included with every new release of the COSMIC database (https://cancer.sanger.ac.uk/). Citation Format: Zbyslaw Sondka, Helen E. Speedy, Sally Bamford, Charlotte G. Cole, Sari A. Ward, Simon A. Forbes. The COSMIC Cancer Gene Census - a comprehensive study of all mutated cancer-driving genes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2469.