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

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

Authors:	Bailey, M. H.; Meyerson, W. U.; Dursi, L. J.; 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, M. C.; Wheeler, D. A.; Getz, G.; Simpson, J. T.; Gerstein, M. B.; Ding, L.; PCAWG Consortium
Contributors:	Abeshouse, A.; Al-Ahmadie, H.; Armenia, J.; Chen, H. W.; Davidson, N. R.; Gao, J.; Ghossein, R.; Giri, D. D.; Gundem, G.; Heins, Z.; Huse, J.; Iacobuzio-Donahue, C. A.; Kahles, A.; Kandoth, C.; King, T. A.; Kundra, R.; Lehmann, K. V.; Levine, D.; Liu, E. M.; Ochoa, A.; Pastore, A.; Rätsch, G.; Reis-Filho, J.; Reuter, V.; Roehrl, M. H. A.; Sanchez-Vega, F.; Sander, C.; Schultz, N.; Senbabaoglu, Y.; Singer, S.; Socci, N. D.; Stark, S. G.; Vázquez-García, I.; Yellapantula, V. D.; Zhang, H.
Article Title:	Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
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. © 2020, The Author(s).
Keywords:	controlled study; human tissue; retrospective studies; gene mutation; exon; genetics; missense mutation; mutation; exons; comparative study; molecular genetics; neoplasm; neoplasms; allele; genetic variability; retrospective study; clonal variation; human genome; genome; dna flanking region; bioinformatics; genome, human; genetic heterogeneity; sampling; genetic database; databases, genetic; heterogeneity; clonal evolution; indel mutation; base composition; exome; spacer dna; dna, intergenic; cancer; humans; human; article; whole genome sequencing; evaluation study; whole exome sequencing; dna base composition; oncogenomics; malignant neoplasm
Journal Title:	Nature Communications
Volume:	11
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2020-09-21
Start Page:	4748
Language:	English
DOI:	10.1038/s41467-020-18151-y
PUBMED:	32958763
PROVIDER:	scopus
PMCID:	PMC7505971
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079069163&doi=10.1038%2fs41467-020-18151-y&partnerID=40&md5=eb26fbba0803afb5b34becf4326298b2
Notes:	Article -- Erratum issued, see DOI: 10.1038/s41467-020-20128-w -- Export Date: 6 August 2021 -- Source: Scopus