OncoKB: Annotation of the oncogenic effect and treatment implications of somatic mutations in cancer.

Abstract

11583 Background: Sequencing of tumor DNA is becoming part of routine clinical care, with the goal of matching patients to approved treatments or clinical trials based on specific mutations. However, interpretation of the clinical implications of identified variants remains a challenge for the treating oncologist, and currently there is no comprehensive database integrated within clinical care that reliably annotates actionable mutations. To address this, we developed OncoKB, a knowledgebase for the oncogenic effects and treatment implications of cancer gene alterations. Methods: With a network of clinical and research fellows, as well as faculty members at Memorial Sloan Kettering Cancer Center (MSK), we have curated detailed information about common cancer genes and their alterations, using diverse sources such as FDA-, NCCN- and other guidelines, ClinicalTrials.gov and the scientific literature. For each variant, the biological effect, prevalence and prognostic information, as well as treatment implications and available clinical trials were collected in a tumor type-specific way. Treatment information was classified by level of evidence, ranging from standard of care to investigational or hypothetical treatments. Results: To date, information on 2,941 unique variants in 417 genes implicated in cancer has been captured in OncoKB (Table 1). Specific alterations in 13 genes are linked to standard and approved therapies, and 32 genes have alterations with emerging evidence for drug sensitivity with the potential to guide patient enrollment for clinical trials. Conclusions: Based on MSK best practices, OncoKB offers oncologists detailed information about individual mutations found in cancer and enables them to make treatment decisions. The information is used in MSK clinical sequencing reports and in OncoVantageTM reports by Quest Diagnostics. Annotated variants, their biological effect and associated level of evidence will be publicly available at oncokb.org and via the cBioPortal for Cancer Genomics. OncoKB Metrics, 2/2/16. Genes Variants Standard Of Care 11 56 Strong Clinical Evidence 32 428 Hypothetical Therapeutic Implications 106 529 Biological Information Only 375 1764