要真正实现肿瘤个体化用药,对癌症序列变异的临床相关性进行分类和筛选是至关重要的.临床基因组资源(ClinGen)的体细胞工作组(WG),与ClinVar和多种癌症变异策展利益相关者合作,已经开发了一套共识的最小变异水平数据(MVLD)。MVLD是一个标准化数据元素的框架,用于临床应用癌症变异。随着MVLD标准的实施,并与ClinVar合作,我们的目标是简化社区中的体细胞变异治疗工作,减少临床实践中癌症变异解释的冗余和时间负担.
我们通过共识方法开发了MVLD,i)回顾了参与工作组的机构的临床可操作性解释,ii)对临床躯体解释模式进行广泛的文献检索,和iii)癌症变异门户网站调查。即将发布的癌症变异解释指南,来自分子病理学协会(AMP),可以并入MVLD。
除了统一由许多数据库收集的等位基因解释性和描述性字段的标准化术语外,MVLD包括癌症变异的独特领域,如生物标志物类,治疗背景和效果。此外,MVLD包括对受控语义和本体的建议。体细胞WG正在与ClinVar合作,评估MVLD在体细胞变体提交中的使用。ClinVar是一个开放且集中的存储库,测序实验室可以在其中报告具有临床意义的摘要级变异数据。ClinVar接受癌症变异数据。
我们希望使用MVLD简化癌症变异的临床解释,增强多个冗余策展工作之间的互操作性,并增加对ClinVar的体细胞变异,所有这些都将增强临床肿瘤学实践的翻译。
To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a
consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice.
We developed MVLD through a
consensus approach by i) reviewing clinical actionability interpretations from institutions participating in the WG, ii) conducting extensive literature search of clinical somatic interpretation schemas, and iii) survey of cancer variant web portals. A forthcoming
guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP), can be incorporated into MVLD.
Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data.
We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of somatic variants to ClinVar, all of which will enhance translation to clinical oncology practice.