Advanced Molecular Diagnostics Laboratory, Princess Margaret Cancer Centre, University Health Network, Toronto, ON.
Department of Clinical Laboratory Genetics, Laboratory Medicine Program, University Health Network, Toronto, ON.
Curr Oncol. 2019 Dec;26(6):353-360. doi: 10.3747/co.26.5281. Epub 2019 Dec 1.
Practices in somatic variant interpretation and classification vary between Canadian clinical molecular diagnostic laboratories, and understanding of current practices and perspectives is limited. To define gaps and future directions, including consensus guideline development, the Somatic Curation and Interpretation Across Laboratories (social) project examined the present state of somatic variant interpretation in Canadian molecular laboratories, including testing volumes and methods, data sources and evidence criteria, and application of published classification guidelines.
Individuals who perform somatic variant interpretation in Canadian centres were invited to participate in an online survey. Invitees included laboratory directors (certified as Fellows of the Canadian College of Medical Geneticists or the American College of Medical Geneticists), md or md and phd molecular pathologists, and other phd experts, including phd specialists in variant annotation or bioinformatics. Current testing methods, volumes, and platforms in next-generation sequencing, use of variant annotation resources and evidence criteria, and preference for variant classification schemes were evaluated.
Responses were received from 37 participants in 8 provinces. A somatic variant classification scheme jointly supported by the Association for Molecular Pathology (amp), the American Society of Clinical Oncology (asco), and the College of American Pathologists (cap) was used by 47% of respondents; an alternative guideline or a combination of published guidelines was used by 35% of respondents. The remaining 18% did not use a published scheme. Only 41% of respondents used a published scheme without alteration. Although all respondents indicated that there is a need for Canadian laboratories to adopt a somatic variant classification guideline, only 38% of respondents felt that it should be mandatory to adopt the amp/asco/cap-endorsed guideline.
Data from the social project identified high variability in current practice, yet strong support for standardization of solid-tumour somatic variant interpretation across Canadian institutions. Aligning classification methods will reduce variation in cross-institutional classification and reporting practices, aiding in consistent practice nationwide.
加拿大临床分子诊断实验室之间的体细胞变异解释和分类实践存在差异，对当前实践和观点的理解有限。为了确定差距和未来方向，包括共识指南的制定，体细胞变异解释和跨实验室分类（SOCIAL）项目检查了加拿大分子实验室体细胞变异解释的现状，包括测试量和方法、数据来源和证据标准，以及发表的分类指南的应用。
邀请在加拿大中心进行体细胞变异解释的个人参与在线调查。邀请对象包括实验室主任（认证为加拿大医学遗传学院或美国医学遗传学院研究员）、医学博士或医学博士和博士分子病理学家，以及其他博士专家，包括变异注释或生物信息学的博士专家。评估了当前的测试方法、下一代测序的量和平台、变异注释资源和证据标准的使用，以及对变异分类方案的偏好。
收到了来自 8 个省的 37 名参与者的回复。47%的受访者使用了由分子病理学协会（AMP）、美国临床肿瘤学会（ASCO）和美国病理学家学院（CAP）联合支持的体细胞变异分类方案；35%的受访者使用了替代指南或发表指南的组合。其余 18%的人没有使用发表的方案。只有 41%的受访者使用未经修改的发表方案。虽然所有受访者都表示加拿大实验室需要采用体细胞变异分类指南，但只有 38%的受访者认为应该强制采用 AMP/ASCO/CAP 认可的指南。
SOCIAL 项目的数据表明，当前实践存在高度差异，但强烈支持加拿大各机构标准化实体肿瘤体细胞变异解释。使分类方法保持一致将减少跨机构分类和报告实践中的差异，有助于全国范围内的一致实践。
