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

Published version
Peer-reviewed

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Authors

Meyerson, William U 
Dursi, Lewis Jonathan  ORCID logo  https://orcid.org/0000-0002-4697-798X

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.

Description

Keywords

Base Composition, DNA, Intergenic, Databases, Genetic, Exome, Exons, Genome, Human, Humans, Mutation, Neoplasms, Retrospective Studies, Exome Sequencing, Whole Genome Sequencing

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

11

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (23916)
Cancer Research UK (23917)
Medical Research Council (MC_UU_12022/2)