文章：

突变癌症驱动基因汇编

A compendium of mutational cancer driver genes

原文发布日期：2020-08-10

DOI: 10.1038/s41568-020-0290-x

类型: Review Article

开放获取: 否

英文摘要：

A fundamental goal in cancer research is to understand the mechanisms of cell transformation. This is key to developing more efficient cancer detection methods and therapeutic approaches. One milestone towards this objective is the identification of all the genes with mutations capable of driving tumours. Since the 1970s, the list of cancer genes has been growing steadily. Because cancer driver genes are under positive selection in tumorigenesis, their observed patterns of somatic mutations across tumours in a cohort deviate from those expected from neutral mutagenesis. These deviations, which constitute signals of positive selection, may be detected by carefully designed bioinformatics methods, which have become the state of the art in the identification of driver genes. A systematic approach combining several of these signals could lead to a compendium of mutational cancer genes. In this Review, we present the Integrative OncoGenomics (IntOGen) pipeline, an implementation of such an approach to obtain the compendium of mutational cancer drivers. Its application to somatic mutations of more than 28,000 tumours of 66 cancer types reveals 568 cancer genes and points towards their mechanisms of tumorigenesis. The application of this approach to the ever-growing datasets of somatic tumour mutations will support the continuous refinement of our knowledge of the genetic basis of cancer.

摘要翻译： 

癌症研究的一个基本目标是理解细胞转化的机制。这是开发更有效的癌症检测方法和治疗策略的关键。实现这一目标的一个里程碑是识别所有能够驱动肿瘤的突变基因。自20世纪70年代以来，癌症基因的数量持续增长。由于癌症驱动基因在肿瘤发生过程中受到正选择作用，它们在队列肿瘤中观察到的体细胞突变模式会偏离中性突变形成的预期模式。这些构成正选择信号的偏差，可以通过精心设计的生物信息学方法进行检测，这类方法已成为鉴定驱动基因的前沿技术。通过系统整合多种信号的方法，有望构建出完整的突变癌症基因汇编。本篇综述中，我们介绍了整合肿瘤基因组学（IntOGen）流程——该方法的一种实践应用，用于获取突变癌症驱动基因的汇编。将其应用于66种癌症类型、超过28,000个肿瘤的体细胞突变数据后，共发现568个癌症基因并揭示了其肿瘤发生机制。随着肿瘤体细胞突变数据集的不断扩展，该方法的持续应用将推动我们对癌症遗传基础认知的持续深化。

原文链接：

A compendium of mutational cancer driver genes