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Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists

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Widespread clinical laboratory implementation of next-generation sequencing–based cancer testing has highlighted the importance and potential benefits of standardizing the interpretation and reporting of molecular results among laboratories. A multidisciplinary working group tasked to assess the current status of next-generation sequencing–based cancer testing and establish standardized consensus classification, annotation, interpretation, and reporting conventions for somatic sequence variants was convened by the Association for Molecular Pathology with liaison representation from the American College of Medical Genetics and Genomics, American Society of Clinical Oncology, and College of American Pathologists. On the basis of the results of professional surveys, literature review, and the Working Group's subject matter expert consensus, a four-tiered system to categorize somatic sequence variations based on their clinical significances is proposed: tier I, variants with strong clinical significance; tier II, variants with potential clinical significance; tier III, variants of unknown clinical significance; and tier IV, variants deemed benign or likely benign. Cancer genomics is a rapidly evolving field; therefore, the clinical significance of any variant in therapy, diagnosis, or prognosis should be reevaluated on an ongoing basis. Reporting of genomic variants should follow standard nomenclature, with testing method and limitations clearly described. Clinical recommendations should be concise and correlate with histological and clinical findings.

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Supported by the Association for Molecular Pathology.

Disclosures: E.J.D. is the Medical Director for Cofactor Genomics and claims ownership in P&V Licensing, LLC; A.Y. is a consultant for Foundation Medicine; A.M.T. received research funding from Foundation Medicine, EMD Serono, Baxalta, Bayer, and Onyx.

The Interpretation of Sequence Variants in Somatic Conditions Working Group is a working group of the Association for Molecular Pathology Clinical Practice Committee with liaison representation from the American College of Medical Genetics and Genomics (S.K. and D.J.W.), American Society of Clinical Oncology (A.M.T. and A.Y), and College of American Pathologists (M.D. and N.I.L.). The 2015 and 2016 Clinical Practice Committee consisted of Marina Nikiforova (Chair 2015 to 2016), Monica Basehore, Christopher Coldren, Linda Cook, Jennifer Crow, Birgit Funke, Meera Hameed, Larry Jennings, Arivarasan Karunamurthy, Annette Kim, Bryan Krock, Mary Lowery-Nordberg, Melissa Miller, Benjamin Pinsky, Somak Roy, Mark Routbort, Ryan Schmidt, and David Viswanatha.

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