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

Publication ,  Journal Article
Bailey, MH; Meyerson, WU; Dursi, LJ; Wang, L-B; Dong, G; Liang, W-W; Weerasinghe, A; Li, S; Li, Y; Kelso, S; MC3 Working Group, ; Saksena, G ...
Published in: Nat Commun
September 21, 2020

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 21, 2020

Volume

11

Issue

1

Start / End Page

4748

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Retrospective Studies
  • Neoplasms
  • Mutation
  • Humans
  • Genome, Human
  • Exons
  • Exome Sequencing
  • Exome
  • Databases, Genetic
 

Citation

APA
Chicago
ICMJE
MLA
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Bailey, M. H., Meyerson, W. U., Dursi, L. J., Wang, L.-B., Dong, G., Liang, W.-W., … PCAWG Consortium, . (2020). Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nat Commun, 11(1), 4748. https://doi.org/10.1038/s41467-020-18151-y
Bailey, Matthew H., William U. Meyerson, Lewis Jonathan Dursi, Liang-Bo Wang, Guanlan Dong, Wen-Wei Liang, Amila Weerasinghe, et al. “Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.Nat Commun 11, no. 1 (September 21, 2020): 4748. https://doi.org/10.1038/s41467-020-18151-y.
Bailey MH, Meyerson WU, Dursi LJ, Wang L-B, Dong G, Liang W-W, et al. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nat Commun. 2020 Sep 21;11(1):4748.
Bailey, Matthew H., et al. “Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.Nat Commun, vol. 11, no. 1, Sept. 2020, p. 4748. Pubmed, doi:10.1038/s41467-020-18151-y.
Bailey MH, Meyerson WU, Dursi LJ, Wang L-B, Dong G, Liang W-W, Weerasinghe A, Li S, Li Y, Kelso S, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Saksena G, Ellrott K, Wendl MC, Wheeler DA, Getz G, Simpson JT, Gerstein MB, Ding L, PCAWG Consortium. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nat Commun. 2020 Sep 21;11(1):4748.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 21, 2020

Volume

11

Issue

1

Start / End Page

4748

Location

England

Related Subject Headings

  • Whole Genome Sequencing
  • Retrospective Studies
  • Neoplasms
  • Mutation
  • Humans
  • Genome, Human
  • Exons
  • Exome Sequencing
  • Exome
  • Databases, Genetic