Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
Faculty of Medicine, University of Southampton, Southampton, UK.
J Med Genet. 2019 Jun;56(6):347-357. doi: 10.1136/jmedgenet-2018-105872. Epub 2019 Apr 8.
The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.
目前用于描述遗传变异及其后果的词汇反映了多年来对高外显率单基因疾病的研究和发现。随着高通量大规模平行测序平台的广泛应用，基因检测的迅速普及，准确的变异解释已成为一个主要问题。用于描述计算机模拟、体外、体内和作为人类疾病致病因素的单基因突变的词汇在使用上是通用的，但在所有这些上下文中的含义不一定相同。在癌症基因检测中，使用肿瘤 DNA 基因测序数据来指导治疗的附加维度对于非癌症遗传学专家来说是一个额外的混淆来源。用于描述癌症易感性基因检测中发现的变异的术语通常仍然反映了孟德尔遗传的过时模式，具有二分结果。癌症是一种常见疾病，具有复杂的遗传结构；需要改进词汇表，以便更好地在科学家、临床医生和患者之间交流，更好地交流遗传变异检测的风险和影响。本综述源于对专注于乳腺癌-卵巢癌易感性基因中变异分类的 ENIGMA 国际多学科联盟成员在词汇使用方面的不一致性的认识和讨论。它列出了遗传变异解释和报告中常用的词汇，并提出了一个通用词汇框架，可能有助于理解和澄清癌症易感性种系基因检测的临床报告。
