OncoKB: A Precision Oncology Knowledge Base.

Chakravarty D1, Gao J1, Phillips SM1, Kundra R1, Zhang H1, Wang J1, Rudolph JE1, Yaeger R1, Soumerai T1, Nissan MH1, Chang MT1, Chandarlapaty S1, Traina TA1, Paik PK1, Ho AL1, Hantash FM1, Grupe A1, Baxi SS1, Callahan MK1, Snyder A1, Chi P1, Danila D1, Gounder M1, Harding JJ1, Hellmann MD1, Iyer G1, Janjigian Y1, Kaley T1, Levine DA1, Lowery M1, Omuro A1, Postow MA1, Rathkopf D1, Shoushtari AN1, Shukla N1, Voss M1, Paraiso E1, Zehir A1, Berger MF1, Taylor BS1, Saltz LB1, Riely GJ1, Ladanyi M1, Hyman DM1, Baselga J1, Sabbatini P1, Solit DB1, Schultz N1.

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Abstract

PURPOSE:

With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, there is an urgent need for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base.

METHODS:

OncoKB annotates the biological and oncogenic effect and the prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response based on US Food and Drug Administration (FDA) labeling, National Comprehensive Cancer Network (NCCN) guidelines, disease-focused expert group recommendations and the scientific literature.

RESULTS:

To date, over 3000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public web resource (http://oncokb.org/) and are also incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers.

CONCLUSION:

OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.