Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Abstract

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.

Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse

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APOBEC3A drives acquired resistance to targeted therapies in non-small cell lung cancer

“…Library preparation and Illumina paired-end sequencing (2 ´ 150 bp) was performed by the Broad Institute Genomics Platform. Sequencing was analyzed using the published Broad Institute pipelines 22,47 . Reads were aligned to the human genome (build hg19) using bwa 48 , then processed through the Picard pipeline (http://broadinstitute.github.io/picard) to recalibrate base quality scores, sort reads, mark duplicate reads, and perform indel realignment.…”

Data Processing Thresholds for Abundance and Sparsity and Missed Biological Insights in an Untargeted Chemical Analysis of Blood Specimens for Exposomics

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