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

Research output: Contribution to journalArticle


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.


  • Matthew H. Bailey
  • William U. Meyerson
  • Lewis Jonathan Dursi
  • Liang Bo Wang
  • Guanlan Dong
  • Wen Wei Liang
  • Amila Weerasinghe
  • Shantao Li
  • Sean Kelso
  • Gordon Saksena
  • Kyle Ellrott
  • Michael C. Wendl
  • David A. Wheeler
  • Gad Getz
  • Jared T. Simpson
  • Mark B. Gerstein
  • Li Ding
  • Rehan Akbani
  • Pavana Anur
  • Matthew H. Bailey
  • Alex Buchanan
  • Kami Chiotti
  • Kyle Covington
  • Allison Creason
  • Yu Fan
  • Steven Foltz
  • Walker Hale
  • David Haussler
  • Julian M. Hess
  • Carolyn M. Hutter
  • Cyriac Kandoth
  • Katayoon Kasaian
  • Melpomeni Kasapi
  • Ake Borg
  • Ian J. Davis
  • Anna Ehinger
  • Dominik Glodzik
  • Dorthe Grabau
  • Mi Ni Huang
  • Peter A. Johansson
  • Erik Larsson
  • Chang Li
  • Jun Li
  • Peter Möller
  • Markus Ringnér
  • Lei Song
  • Johan Staaf
  • Jian Wang
  • Qi Wang
  • Derek W. Wright
  • Yang Yang
  • Fan Zhang
  • Jing Zhang
  • Yan Zhang
  • MC3 Working Group
  • PCAWG novel somatic mutation calling methods working group
  • PCAWG Consortium
External organisations
  • Washington University in St. Louis
  • Yale University
  • Ontario Institute for Cancer Research
  • Hospital for Sick Children, Toronto
  • University of Texas
  • Oregon Health & Science University
  • Baylor College of Medicine
  • Broad Institute
  • Harvard Medical School
  • Massachusetts General Hospital
  • University of California, Santa Cruz
  • National Human Genome Research Institute
  • Memorial Sloan-Kettering Cancer Center
  • British Columbia Cancer Agency
  • University of North Carolina
  • Wellcome Trust Sanger Institute
  • Duke–NUS Medical School
  • QIMR Berghofer Medical Research Institute
  • University of Gothenburg
  • Beijing Genomics Institute
  • China National Genebank
  • University Hospital of Ulm
  • National Cancer Institute, USA
  • German Cancer Research Centre
  • Glasgow Royal Infirmary
  • Peking University
  • Ohio State University
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Medical Genetics
Original languageEnglish
Article number4748
JournalNature Communications
Issue number1
Publication statusPublished - 2020 Sep 21
Publication categoryResearch