ICGC/TCGA团队对整个基因组进行全癌分析。这一研究成果在线发表在2020年2月5日的国际学术期刊《自然》上。
他们从国际癌症基因组联合会（ICGC）和癌症基因组图谱（TCGA）的全基因组（PCAWG）联合会的全癌分析中报告了38个肿瘤类型中2,658个全癌基因组及其匹配的正常组织的综合分析。他们描述了通过使用计算云进行国际数据共享来促进PCAWG资源的生成。平均而言，结合编码和非编码基因组元件时，癌症基因组包含4-5个驱动程序突变。但是，在大约5％的案例中，没有发现任何驱动程序，这表明癌症驱动程序的发现并不完整。发生在单个灾难性事件中的许多簇状结构变异都出现在染色体上，这通常是肿瘤进化的早期事件。例如，在急性黑色素瘤中，这些事件早于大多数体细胞点突变，并同时影响多个与癌症相关的基因。端粒维持异常的癌症通常起源于复制活性低的组织，并显示出几种将端粒损耗降至关键水平的机制。常见和稀有种系变异体会影响体细胞突变的模式，包括点突变、结构变异和体细胞逆转座。PCAWG联合会的一系列文章描述了非编码突变，这些突变并非在TERT启动子上导致癌症。识别突变过程的新特征导致碱基替换、小片段插入和缺失以及结构变异；分析肿瘤演化的时机和模式；描述了体细胞突变对剪接、表达水平、融合基因和启动子活性的多种转录结果；并评估了癌症基因组的一系列更特异的特征。
据介绍，癌症是由基因改变驱动的，大规模并行测序的出现使得能够以全基因组规模系统记录这种变异。
附：英文原文
Title: Pan-cancer analysis of whole genomes
Author: The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium
Issue&Volume: 2020-02-05
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.
DOI: 10.1038/s41586-020-1969-6
Source: https://www.nature.com/articles/s41586-020-1969-6
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
