生物
基因组
癌症
计算生物学
选择(遗传算法)
突变积累
机制(生物学)
积极选择
遗传学
基因
计算机科学
认识论
哲学
人工智能
作者
Stefan C. Dentro,Ignaty Leshchiner,Kerstin Haase,Maxime Tarabichi,Jeff Wintersinger,Amit G. Deshwar,Kaixian Yu,Yulia Rubanova,Geoff Macintyre,Jonas Demeulemeester,Ignacio Vázquez-Garćıa,Kortine Kleinheinz,Dimitri Livitz,Salem Malikić,Nilgun Donmez,Subhajit Sengupta,Pavana Anur,Clemency Jolly,Marek Cmero,Daniel Rosebrock
出处
期刊:Cell
[Cell Press]
日期:2021-04-01
卷期号:184 (8): 2239-2254.e39
被引量:407
标识
DOI:10.1016/j.cell.2021.03.009
摘要
Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.
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