Whole-exome sequencing (WES)

Overview

Capture-based sequencing of the protein-coding portion of the genome (~1–2% of the genome), used in the corpus for driver discovery, mutational signature analysis, copy-number, and neoantigen prediction.

Used by

  • PMID:35927489 — 984 WES CLL samples within the integrated CLL-map cohort (WES/WGS n=1,074); supported the nomination of 82 putative CLL drivers from recurrent sSNV/indels and 6 additional CLUMPS-nominated drivers PMID:35927489.
  • PMID:36723991 — WES on 36 cHL cases complementing 25 WGS cases for the combined 61-patient driver-gene cohort, recovering 26 mutated driver genes/hotspots in classic Hodgkin lymphoma PMID:36723991.
  • PMID:36862133 — whole-exome recapture on 62 ovarian GCT tumor/normal pairs from 59 patients in the Make-an-IMPACT program; uncovered a near-haploid genomic profile in 17% of female germ cell tumors, mutually exclusive with 12p gain PMID:36862133.
  • PMID:37084736 — WES subcohort within the LUAD organotropism study supported APOBEC mutational signature analysis (SBS2/SBS13 18% in metastases vs 8% in primaries, p=0.012, particularly enriched in liver metastases) PMID:37084736.
  • PMID:37202560 — WES on AC-ICAM colon cancer cohort (n=348) for neoantigen prediction and immunoediting quantification, refining the prognostic value of the ICR signature PMID:37202560.
  • PMID:34433969 — WES (median 191X) on 121 fresh-frozen meningiomas from the University Health Network Brain Tumor BioBank; combined with EPIC methylation array, mRNA-seq, and snRNA-seq to define four stable molecular groups (MG1–MG4) for meningioma classification PMID:34433969.
  • PMID:37406106 — WES applied to a subset of HER2-positive metastatic esophagogastric cancer patients in the phase II trial cohort; complemented scRNA-seq and 89Zr-trastuzumab PET/CT PMID:37406106.
  • PMID:37730754 — WES used at Institut Curie for rhabdomyosarcoma patients (n=15); combined with targeted DNA (Dragon panel) PMID:37730754.
  • PMID:38117484 — WES on 64 glioma patients (with WGS or WES) in the GLASS International consortium; integrated with 450K/EPIC methylation arrays and RNA-seq PMID:38117484.
  • PMID:38412093 — WES on 132 of 141 characterized anaplastic thyroid carcinoma regions from 292 patients across 15 institutions PMID:38412093.
  • PMID:38630790 — WES on 3 diffuse pleural mesothelioma cases with genomic near-haploidization PMID:38630790.
  • PMID:38653864 — WES on 33 of 34 evaluable dMMR/MSI-H/hypermutated gynecologic cancer tumors on nivolumab phase 2 trial; complemented MSK-IMPACT and multiplexed immunofluorescence PMID:38653864.
  • PMID:38758238 — WES on 26 pituitary neuroendocrine tumors in the retrospective cohort for USP8 mutation detection; complemented MSK-IMPACT and FACETS LOH analysis PMID:38758238.
  • PMID:38895302 — single-cell clonal expansion followed by WES on 182 melanocytes from normal skin biopsies of tanning bed users and controls; paired with RNA-seq using G&T-seq protocol PMID:38895302.
  • PMID:38949888 — WES on 48 prostate cancer tumor samples (20 MSI-H/dMMR, 28 TMB-H/MSS) via recapture of MSK-IMPACT libraries PMID:38949888.
  • PMID:39091884 — WES at ~95X coverage on 137 keratinocytes, 131 melanocytes, and 23 fibroblasts from 22 skin biopsies via single-cell clonal expansion; profiled AK-to-cSCC evolutionary trajectories PMID:39091884.
  • PMID:27806376 — bulk WES used for subclonal mutation calling (ABSOLUTE) in 6 IDH-mutant oligodendrogliomas; identified inferred-CNV subclones and 22 subclonal point mutations to confirm that the developmental hierarchy is not driven by any single genetic clone PMID:27806376.
  • PMID:35764743 — WES-based HRD classification methodology informed the SigMA/COSMIC SBS3 detection approach applied to MSK-IMPACT data for 444 HGSOC patients; WES is the gold-standard comparator for SBS3 calling from targeted panels in this study PMID:35764743.
  • PMID:39746944 — WES validation set (n=582 NGS libraries) from the MiMSI test cohort re-captured with whole-exome sequencing probes and reanalyzed with the MiMSI classifier; 98.6% concordance with MSK-IMPACT classifications (5 discordant cases), demonstrating that MiMSI generalizes to WES without retraining PMID:39746944.
  • PMID:39975212 — WES (NimbleGen SeqCap EZ Exome+UTR or KAPA HyperExome V1) performed on 297 clonally expanded single melanocytes from 58 skin biopsies; aligned to hg19 with BWA-MEM v2.0.5 and GATK v4.1.2.0; identified bimodal UV-burden (HighMut SBS7, LowMut SBS1/SBS5) subpopulations coexisting in the same skin biopsy PMID:39975212.
  • Used on 55 metastatic breast cancer patients (51 primaries, 102 metastases) in the AURORA cohort; 88/153 specimens had all four assays (WES, WGS, RNA-seq, EPIC array) PMID:36585450
  • Applied to 12 myoepithelioma (MEC) tumor samples from 2 patients (mean coverage 98.5x); revealed chromoplexy-driven structural rearrangements and low TMB (mean 1.35 mutations/Mb) PMID:36577525
  • Applied to 22 primary-metastasis bladder cancer pairs (tumor purity >=25% by FACETS); mean mutational concordance only 42% (range 6%-84%), demonstrating early branched evolution PMID:36543146
  • Used to sequence 10 sporadic PanNETs (Illumina GAIIx with SureSelect capture, mean 101x coverage) in the Johns Hopkins discovery cohort; identified MEN1, DAXX, and ATRX as major driver genes PMID:21252315
  • Applied to 316 HGSOC tumors with matched normals (~180,000 exons, ~18,500 genes) in the TCGA ovarian carcinoma study; TP53 mutated in 96% of sequenced tumors PMID:21720365
  • Applied to 14 NHL cases (DLBCL and FL) with matched tumor/normal pairs in the BCGSC sequencing study; 113 additional cases sequenced via RNA-seq PMID:21796119
  • Used to sequence 74 HNSCC tumors (150x mean coverage, 87% loci >20x) in the Broad Institute HNSCC study; identified 39 significantly mutated genes including NOTCH1 and TP53 PMID:21798893
  • Used to sequence 32 primary HNSCC tumors with matched normals at JHU (Illumina GAIIx/HiSeq 77x and SOLiD 44x); identified NOTCH1 as the second most frequently mutated gene (15%) with predominantly truncating mutations PMID:21798897
  • Applied to 102 breast cancer samples to discover recurrent SF3B1 mutations and characterize the somatic mutational landscape PMID:22158541
  • Applied to 19 pancreatic cystic neoplasms to identify somatic mutations in VHL, RNF43, and GNAS across IPMN, MCN, and SPN subtypes PMID:22158988
  • Applied to 55 DLBCL tumors at the Broad Institute to identify recurrently mutated genes via MutSig analysis PMID:22343534
  • WES complemented WGS in characterizing somatic coding mutations in 65 BCCRC breast tumors PMID:22495314
  • WES of 112 prostate adenocarcinoma tumors (Broad) identified SPOP, FOXA1, and MED12 as recurrent drivers PMID:22610119
  • Used for WES of 100 breast cancer tumors in the Sanger cohort (brca_sanger), identifying ~40 driver genes PMID:22722201
  • Used for WES of 103 breast cancer tumors in the Broad cohort (brca_broad), identifying PIK3CA mutations and MAGI3-AKT3 fusions PMID:22722202
  • Used for WES of 112 prostate cancer tumors in the Michigan cohort (prad_mich), identifying ETS fusions and SPOP mutations PMID:22722839
  • 224 of 276 TCGA colorectal carcinoma tumor/normal pairs analyzed by whole-exome sequencing at median 103-fold coverage; identified 24 significantly mutated genes PMID:22810696
  • 121 melanoma tumor/normal pairs (Broad) analyzed by whole-exome sequencing with solution-phase hybrid capture at 103-fold mean target coverage; identified 6 novel melanoma driver genes PMID:22817889
  • 92 medulloblastoma tumor/normal pairs (Broad) sequenced by whole-exome hybrid capture covering 193,094 exons from 18,863 genes at median 106X coverage PMID:22820256
  • 21 pediatric medulloblastoma pairs (ICGC) analyzed by whole-exome sequencing at 68-fold on-target mean coverage; complemented by WGS (n=39) and custom-capture replication set (n=65) PMID:22832583
  • 147 melanoma tumor/normal pairs (Yale) analyzed by whole-exome sequencing (Roche/NimbleGen SeqCap EZ, 22.4 Mb capture, Illumina GAIIx/HiSeq 2000); discovery cohort for RAC1 P29S and PPP6C PMID:22842228
  • Applied to 74 colorectal tumors (Genentech cohort) to discover RSPO2/RSPO3 fusions and characterise the somatic mutation landscape PMID:22895193
  • Applied to 29 SCLC tumors (CLCGP) alongside WGS, revealing universal TP53+RB1 biallelic loss PMID:22941188
  • Applied to 36 SCLC tumors (JHU) to identify recurrent SOX2 and MYCL amplifications PMID:22941189
  • Applied to 178 LUSC tumors (TCGA) to define comprehensive somatic mutation landscape including CDKN2A, TP53, KEAP1, NFE2L2 PMID:22960745
  • Applied to 183 LUAD tumors (Broad) enabling MutSig-driven discovery of EGFR, KRAS, STK11, RBM10, U2AF1, ARID1A as significant drivers PMID:22980975
  • WES applied to 510 breast tumors as part of the TCGA comprehensive molecular portrait; identified PIK3CA, TP53, GATA3, MAP3K1 as top mutated genes PMID:23000897
  • WES of 142 ICGC pancreatic tumors; achieved mean 69x coverage; identified 2.4 somatic mutations per Mb PMID:23103869
  • WES of 240 neuroblastoma tumors from the Broad cohort; low overall somatic mutation burden (~0.6 per Mb) PMID:23334666
  • WES of 44 ETP-ALL tumors from St. Jude; revealed RAS/PI3K pathway mutations in majority of cases PMID:23334668
  • WES of 160 CLL tumors; identified SF3B1, NOTCH1, DDX3X, POT1 as significantly mutated genes PMID:23415222
  • Whole-exome sequencing (SureSelect v2, Illumina HiSeq; mean 83.3× tumor / 85.9× normal) on 149 esophageal adenocarcinoma tumor/normal pairs; mutation calling via MuTect and Indelocator PMID:23525077
  • Whole-exome sequencing (Nimblegen capture, SOLiD or Illumina) of 40 OSCC tumor/normal pairs as part of integrated multi-platform characterization PMID:23619168
  • Whole-exome sequencing (mean 167.50× coverage) on 150 of 200 AML tumor/normal-skin pairs in TCGA AML study; all candidates validated by hybridization-capture deep digital sequencing PMID:23634996
  • Whole-exome sequencing (≥20× depth) on 248 endometrial carcinoma tumor/normal pairs; identified significantly mutated genes including POLE, TP53, PTEN, PIK3CA, CTNNB1, and ARID5B across the four molecular subtypes PMID:23636398
  • Used in 55 of 60 ACC tumor/normal pairs (Agilent SureSelect 51MB capture, Illumina HiSeq 2000); mean exome coverage 106x, 92.4% target at ≥10x; identified 710 validated nonsynonymous mutations and established a low mutation rate of 0.31 non-silent events/Mb PMID:23685749
  • Used in 24 ACC tumor/normal pairs with matched normal salivary-gland parenchyma for somatic mutation discovery; identified 312 somatic mutations (mean 13/exome), including novel SPEN, NOTCH1/2, and FGFR2 mutations PMID:23778141
  • Used in TCGA CCRCC multi-platform characterization for somatic mutation discovery in 417 tumors; yielded 36,353 putative somatic mutations; 83% of WES mutation calls confirmed by whole-genome sequencing in 22-patient validation set PMID:23792563
  • Applied to 291 primary GBM tumor/normal pairs using Agilent SureSelect 50 Mb hybrid capture at 138x mean target coverage on Illumina GA2000/HiSeq; identified 71 significantly mutated genes PMID:24120142
  • Applied to 99 TCC bladder tumors with matched normals on Illumina HiSeq 2000 with Agilent SureSelect Human All Exon 50 Mb capture; identified 37 significantly mutated genes including STAG2 PMID:24121792
  • Applied to 29 MCL tumor/normal pairs and 6 MCL cell lines; identified 25 significantly mutated genes including NOTCH2, NSD2, BIRC3, and ATM PMID:24145436
  • Used for whole-exome sequencing of 32 intrahepatic cholangiocarcinomas and 9 gallbladder carcinomas (discovery screen) on Agilent SureSelect v2.0 + Illumina HiSeq 2000, mean coverage 130×; paired with targeted DNA sequencing for a prevalence screen of 17 driver genes — identified frequent BAP1, ARID1A, PBRM1, and IDH1/IDH2 mutations in IHCH PMID:24185509.
  • Used to sequence FFPE tumors from 45 BRAF V600 metastatic melanoma patients (DeCOG cohort, skcm_broad_brafresist_2012) on Illumina HiSeq at mean 200× (tumor) / 92× (germline), aligned to hg19 — somatic SNVs called with MuTect, indels with Indelocator, annotations with Oncotator; identified resistance alterations in 23/45 (51%) patients PMID:24265153.
  • Used to sequence 23 surgically resected pancreatic neoplasms with acinar differentiation against matched normals, using Agilent SureSelect v4.0 + Illumina HiSeq (mean 131×, hg18 via Eland/CASAVA); identified absence of KRAS mutations and frequent alterations in SMAD4, JAK1, BRAF, and Fanconi-pathway genes PMID:24293293.
  • Used to sequence 151 MPN patients (48 PV, 62 ET, 39 MF; mean 141× coverage) with tumor DNA from granulocytes and constitutional DNA from T cells/buccal swabs — led to discovery of recurrent somatic CALR exon 9 frameshift indels in 70–84% of JAK2/MPL-negative MPN PMID:24325359.
  • Applied in paired initial/recurrent grade II glioma cohort (n=23) at average 125× coverage, enabling detection of somatic mutations down to ~10% variant allele frequency and identification of clonal evolution patterns including TMZ-induced hypermutation PMID:24336570
  • Applied to 177 of 203 multiple myeloma tumor/normal pairs (avg 89× tumor/88× normal; Agilent SureSelect v2 + Illumina HiSeq 76 bp PE); identified 11 significantly mutated genes and showed pervasive subclonal heterogeneity; 90.4% validation rate across 140 re-genotyped mutations PMID:24434212
  • Applied to 103 rhabdomyosarcoma tumor/normal pairs (SOLiD 4 with Agilent SureSelect 37.8 Mb bait on 90 pairs; Illumina HiSeq with SureSelect v2 on 13 pairs) processed with MuTect/MutSig for the Illumina arm; identified recurrent mutations in FBXW7, BCOR, and RAS/PI3K/RTK axis genes PMID:24436047
  • Applied to 130 muscle-invasive bladder carcinoma (BLCA) tumor/normal pairs (186,260 exons, 18,091 genes; mean 100× coverage, ≥82% target bases ≥30×); identified 32 significantly mutated genes including 9 novel cancer SMGs; mean 302 exonic mutations per sample PMID:24476821
  • Applied to 10 ccRCC primary tumors (79 samples, 8–12 regions each) via Agilent SureSelect Human All Exon V4 on Illumina HiSeq (median ≥70× depth) to characterize intratumor heterogeneity; 92.5% of candidate mutations validated by ultra-deep amplicon sequencing PMID:24487277
  • Used for Discovery Cohort of 20 paired ESCC germline/tumor samples (mean coverage 79×) to identify novel significantly mutated genes including FAT1, FAT2, ZNF750, and KMT2D PMID:24686850
  • Referenced in HCC genomics review (Llovet et al.) summarizing WES/WGS-based identification of recurrent drivers (TERT promoter, TP53, CTNNB1) across hepatocellular carcinoma cohorts PMID:24735922
  • Used for whole-exome sequencing of >1,200 HCC patients to characterise the mutational landscape of hepatocellular carcinoma, including TERT, CTNNB1, and TP53 alterations PMID:24798001
  • Used for exome sequencing of 28 thymic epithelial tumors (tumor/normal pairs) to discover the recurrent GTF2I p.Leu404His hotspot mutation enriched in type A/AB thymomas PMID:24816255
  • Applied to 28 TET tumor/normal pairs to identify recurrent GTF2I c.74146970T>A missense mutation; pipeline used Novoalign + GATK + VarScan2 + SnpEff + Annovar PMID:24974848
  • Whole-exome sequencing of 295 gastric adenocarcinomas (stad_tcga_pub) identified 25 significantly mutated genes in non-hypermutated tumors; exome-based mutation rates supported MSI classification and subtype-specific mutation enrichments PMID:25079317
  • WES of 230 lung adenocarcinomas (luad_tcga_pub) at mean 97.6x tumor / 95.8x germline coverage identified 18 significantly mutated genes including novel RIT1 activating mutations and MGA loss-of-function; mean somatic mutation rate 8.87 mutations/Mb PMID:25079552
  • Used to sequence pre-treatment tumors from 50 muscle-invasive urothelial carcinoma patients (mean coverage 121× tumor/130× germline, SureSelect v2 Exome bait, Illumina HiSeq, aligned to hg19) to identify ERCC2 mutations associated with cisplatin response. PMID:25096233
  • Used to sequence 66 primary chromophobe renal cell carcinoma (ChRCC) tumors (NimbleGen VCRome 2.1 42MB bait, Illumina HiSeq, 90% target coverage ≥20×) as part of the TCGA ChRCC project. PMID:25155756
  • Used to characterize seven patient-derived prostate cancer organoid lines (MSK-PCa1–7) from metastatic biopsies (Agilent SureSelectXT2, ~250× nominal, mean ~142×), identifying PTEN, TP53, SPOP, CHD1, and other driver alterations. PMID:25201530
  • Used to sequence 22 gynaecologic carcinosarcomas (17 uterine, 5 ovarian) paired with matched normal; Agilent SureSelect 51 Mb capture, Illumina HiSeq 2000, mean 191× coverage; identified chromatin-remodelling gene mutations in ~two-thirds of cases PMID:25233892
  • Used in discovery cohort of 15 MPNSTs (12 patients) profiled with SNP6.0 and RNA-seq; WES identified EED/SUZ12 loss-of-function alterations in 80% of MPNSTs PMID:25240281
  • Used for 39 aggressive head-and-neck cSCC tumors paired with matched normal lymphocytes; HGSC VCRome 2.1 42 Mb capture, Illumina HiSeq 2000, mean 115× coverage; revealed extreme UV mutation burden (median 61.2 mutations/Mb) and 23 candidate driver genes PMID:25303977
  • Used in nccRCC study (140 tumor-normal pairs + 5 tumor-only); Agilent SureSelect All Exon 50 Mb, Illumina HiSeq 2000, ~82× mean coverage; identified 10 significantly mutated genes in pRCC including MET (15%) and 6 in chRCC PMID:25401301
  • Applied to 128 tumor/blood exomes (SureSelect 50-Mb, HiSeq 2000, mean 103× coverage) in metastatic melanoma patients treated with anti-CTLA-4; high mutational load correlated with long-term clinical benefit (P=0.01 discovery; P=0.009 validation) PMID:25409260
  • 402 of 496 papillary thyroid carcinoma (THPA) tumor/normal pairs sequenced at mean 97×/94.9× depth as part of the TCGA multiplatform characterization; yielded 0.41 non-synonymous mutations/Mb, a low density relative to most carcinomas PMID:25417114
  • Applied to 78 primary gastric adenocarcinomas (mean 167× tumor / 170× normal, Agilent SureSelect, HiSeq 2000) to discover 16 significantly mutated genes and identify a high-clonality (HiC) subtype with significantly shorter survival (adjusted HR 4.69, P=0.0043) PMID:25583476
  • Used for discovery sequencing of 29 AA MSS CRC tumor/normal pairs (custom Agilent SureSelectXT bait library); 2,696 protein-altering mutations detected across 2,156 genes, identifying 20 significantly mutated genes including EPHA6 and FLCN as AA-specific CRC drivers PMID:25583493
  • Applied to 279 HNSC tumors (mean coverage 95×; 82% of target bases ≥30×) as part of TCGA multi-platform profiling; identified 11 significantly mutated genes by MutSigCV including TP53 (72%), FAT1 (23%), PIK3CA (21%), and NOTCH1 (19%) PMID:25631445
  • Used on 34 paired tumor/normal samples from NSCLC patients treated with pembrolizumab (mean target coverage 164×; 94.5% of target ≥10×); higher nonsynonymous mutation burden (cutoff ≥178 mutations) significantly associated with durable clinical benefit and prolonged PFS PMID:25765070
  • Applied Agilent SureSelect whole-exome capture (v2/v3/v4/v5+UTRs) on Illumina HiSeq 2000 to profile 243 HCC tumors at mean 72× depth for somatic mutation and mutational-signature analysis. PMID:25822088
  • Used for somatic SNV/indel discovery in 109 microdissected pancreatic ductal adenocarcinoma cases (TruSeq/Nextera capture, Illumina HiSeq 2500, mean 51× depth); microdissection substantially increased mutation yield versus bulk tissue. PMID:25855536
  • Applied to 10 PCNSL cases (SureSelect 50 Mb, HiSeq2000, mean 65.6M mapped reads, median 80% exome at ≥30×) for somatic SNV and indel calling to identify NF-κB pathway drivers including MYD88 L265P. PMID:25991819
  • SureSelect Exome v4 sequencing at mean 160×/100× (tumor/normal) in 150 mCRPC cases enabled comprehensive somatic profiling revealing 89% actionable alterations. PMID:26000489
  • Applied to 320 cutaneous melanoma samples (Agilent SureSelect Human All Exon v2.0 44 Mb, HiSeq 2×76 bp, ~87× mean coverage) enabling identification of 13 significantly mutated genes including novel DDX3X and four genomic subtypes. PMID:26091043
  • Whole-exome sequencing applied to 91 adrenocortical carcinoma samples to identify somatic mutations and copy-number alterations PMID:26095796
  • Whole-exome sequencing used to characterize somatic mutations in breast cancer genomic study PMID:26168399
  • Whole-exome sequencing used to profile somatic mutations in colorectal cancer PMID:26343386
  • Performed on pretreatment tumor and matched germline DNA from 110 metastatic melanoma patients (skcm_dfci_2015) at mean coverage 183.7x (tumor) / 157.2x (germline); nonsynonymous mutational load (median 197/sample) and predicted neoantigen load were each significantly associated with ipilimumab clinical benefit PMID:26359337
  • Applied to 817 breast tumors (TCGA ILC/IDC study) for somatic mutation calling; identified CDH1 (63% ILC vs 2% IDC), TBX3, RUNX1, PIK3CA, FOXA1 as ILC-enriched drivers and TP53 as IDC-enriched; no CDH1 promoter hypermethylation observed PMID:26451490
  • Applied to 538 CLL samples with matched germline DNA (mean depth 95x); identified 44 recurrently mutated driver genes and 11 recurrent sCNVs; longitudinal WES of 59 matched pre-treatment/relapse pairs showed clonal evolution in 97% (57/59) of cases PMID:26466571
  • Applied to 333 tumor/normal pairs from primary prostate adenocarcinomas (TCGA); identified 13 significantly mutated genes (MutSigCV) and 0.94 mutations/Mb median mutation burden PMID:26544944.
  • Used to sequence tumor-normal pairs from 42 CTCL patients (25 Sézary syndrome, 17 other CTCL) with Agilent SureSelect 50 Mb All Exon kit, mean depth 143.5×; identified recurrent deletions of TP53, RB1, PTEN, DNMT3A and CDKN1B, and mutations in TCR-signaling and epigenetic genes PMID:26551667.
  • Applied to 9 primary uveal melanoma tumors and 5 primary tumor-derived cell lines as part of a 28-sample cohort; recurrent PLCB4 p.D630Y hotspot and canonical UM drivers (GNA11, GNAQ, BAP1, SF3B1, EIF1AX) characterized PMID:26683228.
  • Used for 3 FFPE matched primary/recurrent medulloblastoma pairs (Nextera Rapid Capture) as part of a 46-sample WGS/WES study demonstrating divergent clonal selection at recurrence PMID:26760213.
  • Used for whole-exome sequencing of 160 periampullary tumors (AMPAC, CAC, DUOAC) at ~120× coverage on HiSeq 2000, followed by HGSC Mercury pipeline variant calling, as part of the Australian Pancreatic Cancer Genome Initiative molecular taxonomy study PMID:26804919
  • Applied to 820 diffuse glioma samples from TCGA pan-glioma study (513 LGG + 307 GBM) to identify 75 significantly mutated genes including 45 novel glioma associations PMID:26824661
  • Used for whole-exome sequencing of 114 metastatic biopsies from 81 men with castration-resistant prostate cancer (CRPC-Adeno and CRPC-NE) using SureSelect v2/v4 or HaloPlex Exome at ~100× mean target coverage PMID:26855148
  • Used on 141 tumors from 56 men with metastatic CRPC (prad_fhcrc cohort) with Nimblegen V2/V3 capture on Illumina HiSeq 2000; alignment via bwa v0.7.1 with GATK indel realignment and MuTect somatic calling. PMID:26928463
  • Applied to 38 metastatic melanoma pretreatment biopsies on Illumina HiSeq2000 (2×100 bp; median 140× coverage) to call SNVs/INDELs for anti-PD-1 response analysis PMID:26997480
  • Applied to 619 CRC FFPE tumor/normal pairs (Illumina HiSeq 2000, SureSelect v.2 capture; mean 90× coverage, 87% of bases ≥20×) for driver discovery and neoantigen analysis PMID:27149842
  • Applied to 660 lung ADC and 484 lung SqCC tumor/normal pairs (Agilent SureSelect 50MB, Illumina paired-end) for comprehensive NSCLC driver and neoepitope landscape analysis PMID:27158780
  • Whole-exome sequencing applied in germline susceptibility studies of young-onset NSCLC, including identification of pathogenic variants in BRCA1, BRCA2, and Fanconi-anemia-pathway genes in YLC cohorts PMID:27346245
  • WES applied to a discovery cohort of 19 advanced germ cell tumors (10 cisplatin-resistant, 9 cisplatin-sensitive) at mean 116x coverage; identified TP53 mutations exclusive to resistant tumors and novel RAC1 hotspot mutations validated in the prospective MSK-IMPACT cohort PMID:27646943
  • CLIA-grade EXaCT-1 whole-exome sequencing (Agilent HaloPlex, 21,522 genes, mean 85x coverage) applied to 72 urothelial carcinoma tumours from 32 patients to map clonal evolution pre- and post-chemotherapy. PMID:27749842
  • WES on N=44 B-ALL cases from the DUX4/ERG subtype study (1,913 total cases) to detect sequence mutations; mean 17.5 non-silent mutations per case with a paucity of structural alterations. PMID:27776115
  • Enhanced exome sequencing (NimbleGen v3 capture + 264 AML gene probes, Illumina HiSeq 2000/2500) on 39 AML/MDS patients with 157 serial exomes to track clonal dynamics during decitabine therapy. PMID:27959731
  • Used as a CLIA-certified clinical assay (Agilent SureSelectXT All Exon V5+UTRs, HiSeq2500, paired-end 125 bp × 2) in the PIPseq pediatric precision oncology program; achieved >150-fold average coverage and >98% coding sequence at ≥10× across 82 pediatric tumor/normal pairs PMID:28007021.
  • Applied to 216 metastatic breast cancer tumor-normal pairs (Agilent SureSelect All Exon V5/Clinical Research Exome; Illumina HiSeq 2500/4000 or NextSeq 500; mean 83± 18× normal, 122±15× tumor) to identify 12 significantly mutated driver genes in metastatic breast cancer PMID:28027327.
  • Applied to 164 oesophageal carcinomas and 359 gastric adenocarcinomas in the TCGA esophageal/stomach study (Agilent SureSelect V5 at Broad Institute and Nimblegen SeqCap EZ v3.0 at Washington University) to define squamous vs. adenocarcinoma molecular subtypes PMID:28052061.
  • Applied to 173 pheochromocytoma/paraganglioma tumors in the TCGA PCPG study (paired tumor + matched normal) yielding a somatic mutation rate of ~0.67 mutations/Mb and identifying five significant driver genes PMID:28162975.
  • Applied whole-exome sequencing to characterize somatic mutations in tumor samples PMID:28196596
  • Performed whole-exome sequencing as part of clinical genomic profiling for cancer patients PMID:28336552
  • Applied whole-exome sequencing to identify somatic mutations in pediatric cancer cohort PMID:28445112
  • Whole-exome sequencing of 16 paired tumor-normal clear cell endometrial carcinoma samples (Illumina Truseq and Agilent SureSelect; mean depth 75x) in the uccc_nih_2017 discovery cohort PMID:28485815
  • WES of 327 spatially separated primary NSCLC tumor regions and 4 metastatic biopsies through the TRACERx M-Seq pipeline, used to design bespoke ctDNA monitoring panels (median 18 SNVs/patient) PMID:28445469
  • 106 MSK-IMPACT tumors re-captured with Agilent Exome Kit v3 (mean 240x) for cross-platform TMB validation; WES vs MSK-IMPACT TMB correlation R2=0.76 PMID:28481359
  • Applied to 200 CCA cases as part of the multi-platform ICGC cholangiocarcinoma cohort (489 total tumors), contributing somatic mutation calls to the integrative four-cluster analysis PMID:28667006
  • Used for 101 medulloblastoma cases (from prior PCGP/MAGIC studies) complementing 390 whole-genome sequenced cases in the ICGC PedBrain MAGIC cohort of 491 diagnostic tumor-normal pairs PMID:28726821
  • Applied to 500 adult patients with metastatic solid tumors (MET500 cohort) using Agilent SureSelect Human All Exon v4 (mean 180× tumor / 120× normal coverage), generating the primary somatic variant calls for SNVs (VarScan2), indels (Pindel), and annotations (ANNOVAR) PMID:28783718
  • Used for somatic variant discovery in 1001 de novo DLBCL tumors (400 paired tumor-normal; Agilent All Exon V5, ~75X on Illumina HiSeq 2500) PMID:28985567
  • Applied to 412 chemotherapy-naive muscle-invasive bladder cancer (BLCA) tumor/normal pairs (Agilent SureSelect 50 Mb, mean 85X, 79% target ≥30X) identifying 128,772 SNVs and 2,888 indels PMID:28988769
  • Applied to 68 paired pre- and on-therapy melanoma biopsies (Agilent SureSelect All Exon V2, mean 168X; re-sequenced at 300X for selected responders) to quantify on-therapy somatic mutation and neoantigen loss PMID:29033130
  • Applied to 205 adult soft tissue sarcomas (6 histologies) for somatic mutation analysis; only 3 pan-cohort significantly mutated genes identified (TP53, ATRX, RB1), confirming SCNA-driven biology PMID:29100075
  • Applied to 35 pre-treatment metastatic CCRCC tumor/normal pairs (mean 128× tumor / 91× normal) to identify PBRM1 LOF as an anti-PD-(L)1 response biomarker PMID:29301960
  • Paired WES (n=49) validated that MSK-IMPACT targeted-panel TMB correlates tightly with whole-exome TMB in NSCLC patients treated with anti-PD-(L)1 therapy (Spearman r=0.86, P<0.001) PMID:29337640
  • Used to profile 15 Korean vulvar SCC tumor/normal pairs (Agilent SureSelect Human All Exome V4, BWA/GATK pipeline) for HPV-stratified mutational landscape analysis PMID:29422544
  • Used for trio whole-exome sequencing of 372 pediatric cancer patients to identify germline LP/PVs in 25 HBOC-associated genes (GRCh38/hg38); CNVs were not analyzed PMID:29489754
  • Formed the sequencing backbone of the TCGA MC3 project, processing ~10,510 tumor/normal pairs across 33 cancer types on Illumina platforms with multiple capture kits; intersection-of-capture-kit BED used as exonic mask PMID:29596782
  • Applied to 1,013 prostate tumor/normal pairs (680 primary, 333 metastatic castration-resistant) to define 97 significantly mutated genes; mean target coverage 104.7× (tumor) and 103.8× (normal) PMID:29610475

Notes

  • Several corpus papers explicitly note WES (vs targeted panels) is what enables full mutational-signature decomposition and immunoediting analysis PMID:37084736 PMID:37202560.

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