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

MC3 Working Group, PCAWG novel somatic mutation calling methods working group, PCAWG Consortium, Boris Winterhoff

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Article number4748
JournalNature communications
Issue number1
StatePublished - Sep 21 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).


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

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Comparative Study


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