The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.

癌症基因组图谱 (TCGA) 和国际癌症基因组联盟 (ICGC) 分别使用全外显子组测序 (WES) 和全基因组测序 (WGS) 策划了共识体细胞突变调用。在此，作为 ICGC/TCGA 全基因组泛癌症分析 (PCAWG) 联盟的一部分，该联盟汇总了 38 种肿瘤类型的 2,658 种癌症的全基因组测序数据，我们并排比较了 746 个 TCGA 样本的 WES 和 WGS，发现约 80% 的突变在覆盖的外显子区域重叠。我们估计，低变异等位基因比例 (VAF < 15%) 和克隆异质性贡献了高达 68% 的专用 WGS 突变和 71% 的专用 WES 突变。我们观察到，大约 30% 的私人 WGS 突变可追溯到 WES 共识工作中单个变异调用者识别的突变。 WGS 捕获了外显子区域约 50% 以上的变异以及具有可变 GC 含量的基因座中未观察到的突变。总之，我们的分析强调了两种可重复体细胞变异检测工作之间的技术差异。