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

Author(s): Bailey, Matthew H; Meyerson, William U; Dursi, Lewis J; Wang, Liang-Bo; Dong, Guanlan; et al

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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.
Publication Date: 21-Sep-2020
Citation: Bailey, Matthew H., William U. Meyerson, Lewis Jonathan Dursi, Liang-Bo Wang, Guanlan Dong, Wen-Wei Liang, Amila Weerasinghe, Shantao Li, Yize Li, Sean Kelso, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Gordon Saksena, Kyle Ellrott, Michael C. Wendl, David A. Wheeler, Gad Getz, Jared T. Simpson, Mark B. Gerstein, Li Ding, and PCAWG Consortium. "Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples." Nature Communications 11, no. 1 (2020): 1-27. doi:10.1038/s41467-020-18151-y
DOI: 10.1038/s41467-020-18151-y
EISSN: 2041-1723
Pages: 1 - 27
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Nature Communications
Version: Final published version. This is an open access article.

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