AMP Horizons: Somatic variant curation using OncoKB, an FDA-recognized precision oncology knowledge base

Somatic variant curation using OncoKB, an FDA-recognized precision oncology knowledge base

Large multi-gene NGS panel-based tumor sequencing has emerged as a standard component of patient care in clinical oncology. Over the past two decades, a growing number of molecular events have been established as predictive biomarkers of drug sensitivity or resistance to approved or investigational targeted therapies. The recognition that different mutations even within the same gene often have different biological properties and consequently different drug sensitivities has made it challenging for point-of-care clinicians to interpret the large number of somatic and germline variants that emerge from clinical tumor genomic profiling. As a result, the communication burden of variant-specific therapeutic implications has been increasingly placed onto molecular pathology sequencing laboratories. To address the challenge of clinical variant interpretation, clinical decision support tools such as OncoKB were developed. Evidence-based information that structures the tumor-type specific diagnostic, prognostic, and therapeutic implications of a cancer variant into a database are curated from multiple sources including the FDA drug labels, the NCCN guidelines, and the scientific literature. This information is thus programmatically accessible and available in multiple outputs such as a publicly available website and as variant-specific annotation in clinical sequencing reports. In April 2018, the FDA announced their regulatory approach for the Use of Public Human Genetic Variant Database to support the Agency's precision medicine initiatives. "The goal of this effort is to help ensure patients receive accurate, reliable, and clinically meaningful test results, while promoting innovation in test development".  In October 2021, OncoKB became the first somatic human variant database to be partially recognized by the FDA.

• Conceptual understanding of “Precision Oncology”
• Understanding of why the adoption of precision oncology in both academic cancer centers and community practices generated the need for precision oncology knowledge bases such as OncoKB to serve as clinical decision support tools.
• Understand where knowledge bases such as OncoKB sit within the precision oncology/molecular pathology workflow
• Identify the complexity behind aggregating and standardizing variant annotations from distributed sources
  
• Describe the methods for accessing data in OncoKB, from website portals to programmatic APIs
  
• Outline the hierarchy for data organization to link genes, genetic alterations, indications, and levels of evidence
  

Speaker: Debyani Chakravarty, PhD	Moderator: Adam Fisch, MD

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This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint providership of American Society for Clinical Pathology (ASCP) and Association for Molecular Pathology (AMP). The American Society for Clinical Pathology (ASCP) is accredited by the ACCME to provide continuing medical education for physicians.

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