TY - JOUR
T1 - Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
AU - MC3 Working Group
AU - PCAWG novel somatic mutation calling methods working group
AU - PCAWG Consortium
AU - Bailey, Matthew H.
AU - Meyerson, William U.
AU - Dursi, Lewis Jonathan
AU - Wang, Liang Bo
AU - Dong, Guanlan
AU - Liang, Wen Wei
AU - Weerasinghe, Amila
AU - Li, Shantao
AU - Kelso, Sean
AU - Akbani, Rehan
AU - Anur, Pavana
AU - Bailey, Matthew H.
AU - Buchanan, Alex
AU - Chiotti, Kami
AU - Covington, Kyle
AU - Creason, Allison
AU - Ding, Li
AU - Ellrott, Kyle
AU - Fan, Yu
AU - Foltz, Steven
AU - Getz, Gad
AU - Hale, Walker
AU - Mills, Gordon B.
AU - Wang, Wenyi
AU - Weinstein, John N.
AU - Chen, Ken
AU - Chong, Zechen
AU - Akdemir, Kadir C.
AU - Aldape, Kenneth
AU - Chakravarty, Dimple
AU - Chen, Yiwen
AU - Chong, Zechen
AU - Czerniak, Bogdan
AU - El-Naggar, Adel
AU - Futreal, P. Andrew
AU - Gershenwald, Jeffrey E.
AU - Han, Leng
AU - Huse, Jason
AU - von Kalle, Christof
AU - Krishnamurthy, Savitri
AU - Lazar, Alexander J.
AU - Li, Jun
AU - Liang, Han
AU - Lu, Yiling
AU - Park, Keunchil
AU - Sood, Anil K.
AU - Su, Xiaoping
AU - Van Loo, Peter
AU - Wang, Linghua
AU - Zhu, Hongtu
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-020-18151-y
DO - 10.1038/s41467-020-18151-y
M3 - Article
C2 - 32958763
AN - SCOPUS:85079069163
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4748
ER -