Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
Int J Cancer. 2019 Dec 1;145(11):2996-3010. doi: 10.1002/ijc.32358. Epub 2019 May 21.
Next-generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool in translational oncology. Its rapidly increasing use during the last decade has expanded the options for targeted tumor therapies, and molecular tumor boards have grown accordingly. However, with increasing detection of genetic alterations, their interpretation has become more complex and error-prone, potentially introducing biases and reducing benefits in clinical practice. To facilitate interdisciplinary discussions of genetic alterations for treatment stratification between pathologists, oncologists, bioinformaticians, genetic counselors and medical scientists in specialized molecular tumor boards, several systems for the classification of variants detected by large-scale sequencing have been proposed. We review three recent and commonly applied classifications and discuss their individual strengths and weaknesses. Comparison of the classifications underlines the need for a clinically useful and universally applicable variant reporting system, which will be instrumental for efficient decision making based on sequencing analysis in oncology. Integrating these data, we propose a generalizable classification concept featuring a conservative and a more progressive scheme, which can be readily applied in a clinical setting.
下一代测序已成为癌症精准医学中治疗指导的基石，也是转化肿瘤学中不可或缺的研究工具。在过去十年中，它的使用迅速增加，扩大了靶向肿瘤治疗的选择，分子肿瘤委员会也相应发展。然而，随着遗传改变的检测增加，其解释变得更加复杂和容易出错，这可能会在临床实践中引入偏差并降低获益。为了促进病理学家、肿瘤学家、生物信息学家、遗传咨询师和医学科学家在专门的分子肿瘤委员会中就治疗分层的遗传改变进行跨学科讨论，已经提出了几种用于分类大规模测序检测到的变异的系统。我们回顾了三种最近且常用的分类，并讨论了它们各自的优缺点。对分类的比较强调了需要一个临床上有用且普遍适用的变异报告系统，这对于基于肿瘤学测序分析进行有效的决策至关重要。整合这些数据，我们提出了一个可推广的分类概念，具有保守和更激进的方案，可在临床环境中轻松应用。
