文章：

识别癌症基因组中的上位效应：一项精细的工作

Identifying Epistasis in Cancer Genomes: A Delicate Affair

原文发布日期：2019-05-30

DOI: 10.1016/j.cell.2019.05.005

类型: Perspective

开放获取: 是

英文摘要：

Recent studies of the tumor genome seek to identify cancer pathways as groups of genes in which mutations are epistatic with one another or, specifically, “mutually exclusive.” Here, we show that most mutations are mutually exclusive not due to pathway structure but to interactions with disease subtype and tumor mutation load. In particular, many cancer driver genes are mutated preferentially in tumors with few mutations overall, causing mutations in these cancer genes to appear mutually exclusive with numerous others. Researchers should view current epistasis maps with caution until we better understand the multiple cause-and-effect relationships among factors such as tumor subtype, positive selection for mutations, and gross tumor characteristics including mutational signatures and load.

摘要翻译： 

近期对肿瘤基因组的研究试图将癌症通路定义为基因群，其中突变彼此呈现上位效应，或具体表现为“互斥”关系。本文指出，多数突变之所以互斥，并非由于通路结构本身，而是与疾病亚型和肿瘤突变负荷的相互作用所致。特别是许多癌症驱动基因更倾向于在整体突变较少的肿瘤中发生突变，导致这些癌症基因的突变与众多其他基因的突变呈现出互斥现象。在研究明确肿瘤亚型、突变的正向选择压力以及包括突变特征和负荷在内的整体肿瘤特征之间的多重因果关系之前，学者们应谨慎看待当前的上位效应图谱。

原文链接：

Identifying Epistasis in Cancer Genomes: A Delicate Affair