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OncoKB: A Precision Oncology Knowledge Base
Debyani Chakravarty1, Jianjiong Gao1, Sarah M Phillips1
1, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Breast Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Breast Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Head and Neck Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , , Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA; , Department of R&D and Bioinformatics, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA; , Head and Neck Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Melanoma and Immunotherapeutics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Gynecologic Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Sarcoma Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Sarcoma Medical Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Department of Oncology and Internal Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA , Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; , Breast Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Developmental Therapeutics, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Weill Cornell Medical College, New York, NY USA; , Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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.
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