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

Bailey, Matthew H.; Perry, MD; Puiggros, M; Rheinbay, E; Stebbings, L; Stewart, C; Stobbe, MD; Tiao, G; Wang, J; Waszak, SM; Werner, J; Yamaguchi, TN; Pedersen, JS; Puiggròs, M; Raine, KM; Royo, R; Sahinalp, SC; Sarrafi, I; Schlesner, M; Simpson, JT; Teague, JW; Torrents, D; Wala, JA; Weischenfeldt, J; Wendl, M; Wu, Z; Xue, H; Yakneen, S; Ye, K; Yellapantula, VD; Yung, CK; Zhang, J; Saksena, G; Ellrot, K; Wendl, MC; Wheeler, DA; Aaltonen, LA; Abascal, F; Abeshouse, A; Aburatani, H; Adams, DJ; Agrawal, N; Ahn, KS; Ahn, S-M; Aikata, H; Akbani, R; Akdemir, KC; Al-Ahmadie, H; Al-Sedairy, ST; Al-Shahrour, F; Alawi, M; Albert, M; Aldape, K; Alexandrov, LB; Ally, A; Alsop, K; Alvarez, EG; Amary, F; Amin, SB; Aminou, B; Ammerpohl, O; Anderson, MJ; Ang, Y; Antonello, D; Anur, P; Aparicio, S; Meyerson, William U.; Buchanan, A; Chiotti, K; Covington, K; Creason, A; Ding, L; Ellrott, K; Fan, Y; Foltz, S; Dursi, Lewis Jonathan; Hale, W; Haussler, D; Hutter, CM; Kandoth, C; Kasaian, K; Kasapi, M; Larson, D; Leshchiner, I; Wang, Liang-Bo; Letaw, J; Ma, S; McLellan, MD; Men, Y; Mills, GB; Peto, M; Radenbaugh, A; Reynolds, SM; Dong, Guanlan; Sofia, H; Struck, AJ; Stuart, JM; Wang, W; Weinstein, JN; Wong, CK; Xi, L; Liang, Wen-Wei; Bailey, MH; Niu, B; Bieg, M; Boutros, PC; Buchhalter, I; Butler, AP; Chen, K; Chong, Z; Drechsel, O; Weerasinghe, Amila; Jonathan Dursi, L; Eils, R; Espiritu, SMG; Fulton, RS; Gao, S; Gelpi, JLL; Gerstein, MB; Getz, G; Gonzalez, S; Li, Shantao; Gut, IG; Hach, F; Heinold, MC; Hess, JM; Hinton, J; Hu, T; Huang, V; Huang, Y; Hutter, B; Jones, DR; Kelso, Sean; Jung, J; Jäger, N; Kim, HL; Kleinheinz, K; Kumar, S; Kumar, Y; Lalansingh, CM; Letunic, I; Livitz, D; Ma, EZ; Maruvka, YE; Mashl, RJ; Menzies, A; Milovanovic, A; Nielsen, MM; Ossowski, S; Paramasivam, N; Scarlett, Christopher

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

journal contribution

posted on 2025-05-11, 18:48 authored by Matthew H. Bailey, MD Perry, M Puiggros, E Rheinbay, L Stebbings, C Stewart, MD Stobbe, G Tiao, J Wang, SM Waszak, J Werner, TN Yamaguchi, JS Pedersen, M Puiggròs, KM Raine, R Royo, SC Sahinalp, I Sarrafi, M Schlesner, JT Simpson, JW Teague, D Torrents, JA Wala, J Weischenfeldt, M Wendl, Z Wu, H Xue, S Yakneen, K Ye, VD Yellapantula, CK Yung, J Zhang, G Saksena, K Ellrot, MC Wendl, DA Wheeler, LA Aaltonen, F Abascal, A Abeshouse, H Aburatani, DJ Adams, N Agrawal, KS Ahn, S-M Ahn, H Aikata, R Akbani, KC Akdemir, H Al-Ahmadie, ST Al-Sedairy, F Al-Shahrour, M Alawi, M Albert, K Aldape, LB Alexandrov, A Ally, K Alsop, EG Alvarez, F Amary, SB Amin, B Aminou, O Ammerpohl, MJ Anderson, Y Ang, D Antonello, P Anur, S Aparicio, William U. Meyerson, A Buchanan, K Chiotti, K Covington, A Creason, L Ding, K Ellrott, Y Fan, S Foltz, Lewis Jonathan Dursi, W Hale, D Haussler, CM Hutter, C Kandoth, K Kasaian, M Kasapi, D Larson, I Leshchiner, Liang-Bo Wang, J Letaw, S Ma, MD McLellan, Y Men, GB Mills, M Peto, A Radenbaugh, SM Reynolds, Guanlan Dong, H Sofia, AJ Struck, JM Stuart, W Wang, JN Weinstein, CK Wong, L Xi, Wen-Wei Liang, MH Bailey, B Niu, M Bieg, PC Boutros, I Buchhalter, AP Butler, K Chen, Z Chong, O Drechsel, Amila Weerasinghe, L Jonathan Dursi, R Eils, SMG Espiritu, RS Fulton, S Gao, JLL Gelpi, MB Gerstein, G Getz, S Gonzalez, Shantao Li, IG Gut, F Hach, MC Heinold, JM Hess, J Hinton, T Hu, V Huang, Y Huang, B Hutter, DR Jones, Sean Kelso, J Jung, N Jäger, HL Kim, K Kleinheinz, S Kumar, Y Kumar, CM Lalansingh, I Letunic, D Livitz, EZ Ma, YE Maruvka, RJ Mashl, A Menzies, A Milovanovic, MM Nielsen, S Ossowski, N Paramasivam, Christopher ScarlettChristopher Scarlett

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.

History

Journal title

Nature Communications

Volume

11

Issue

1

Article number

4748

Publisher

Nature

Language

en, English

College/Research Centre

Faculty of Health and Medicine

School

School of Medicine and Public Health

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