Li Marilyn M, Datto Michael, Duncavage Eric J, Kulkarni Shashikant, Lindeman Neal I, Roy Somak, Tsimberidou Apostolia M, Vnencak-Jones Cindy L, Wolff Daynna J, Younes Anas, Nikiforova Marina N
Interpretation of Sequence Variants in Somatic Conditions Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Bethesda, Maryland; Department of Pathology and Laboratory Medicine, Division of Genomic Diagnostics, the Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Interpretation of Sequence Variants in Somatic Conditions Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Bethesda, Maryland; Duke University School of Medicine, Durham, North Carolina.
J Mol Diagn. 2017 Jan;19(1):4-23. doi: 10.1016/j.jmoldx.2016.10.002.
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.
基于新一代测序的癌症检测在临床实验室中的广泛应用凸显了各实验室之间规范分子检测结果解读与报告的重要性及潜在益处。美国分子病理学会联合美国医学遗传学与基因组学学会、美国临床肿瘤学会以及美国病理学家学会的联络代表，召集了一个多学科工作组，负责评估基于新一代测序的癌症检测现状，并为体细胞序列变异制定标准化的共识分类、注释、解读及报告规范。基于专业调查结果、文献综述以及工作组主题专家的共识，提出了一个根据临床意义对体细胞序列变异进行分类的四级系统：一级，具有明确临床意义的变异；二级，具有潜在临床意义的变异；三级，临床意义未知的变异；四级，判定为良性或可能良性的变异。癌症基因组学是一个快速发展的领域；因此，任何变异在治疗、诊断或预后方面的临床意义都应持续重新评估。基因组变异的报告应遵循标准命名法，并清晰描述检测方法及局限性。临床建议应简洁明了，并与组织学和临床发现相关联。
