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

Bailey MH, Meyerson WU, Dursi LJ, Wang LB, Dong G, Liang WW, 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

Nat Commun 11 (1) 4748 [2020-09-21; online 2020-09-21]

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.

Clinical Genomics Uppsala [Service]

QC bibliography QC xrefs

PubMed 32958763

DOI 10.1038/s41467-020-18151-y

Crossref 10.1038/s41467-020-18151-y

pii: 10.1038/s41467-020-18151-y
pmc: PMC7505971