EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100160750EGA dataset EGAD00001001607EGANeuroblastoma is a malignancy of the developing sympathetic nervous system that is often lethal when relapse occurs. We here used whole-exome sequencing, mRNA expression profiling, array CGH and DNA methylation analysis to characterize 16 paired samples at diagnosis and relapse from individuals with neuroblastoma. The mutational burden significantly increased in relapsing tumors, accompanied by altered mutational signatures and reduced subclonal heterogeneity. Global allele frequencies at relapse indicated clonal mutation selection during disease progression. Promoter methylation patterns were consistent over disease course and were patient specific. Recurrent alterations at relapse included mutations in the putative CHD5 neuroblastoma tumor suppressor, chromosome 9p losses, DOCK8 mutations, inactivating mutations in PTPN14 and a relapse-specific activity pattern for the PTPN14 target YAP. Recurrent new mutations in HRAS, KRAS and genes mediating cell-cell interaction in 13 of 16 relapse tumors indicate disturbances in signaling pathways mediating mesenchymal transition. Our data shed light on genetic alteration frequency, identity and evolution in neuroblastoma.Mutational dynamics between primary and relapse neuroblastomas.Schramm Alexander A, Köster Johannes J, Assenov Yassen Y, Althoff Kristina K, Peifer Martin M, Mahlow Ellen E, Odersky Andrea A, Beisser Daniela D, Ernst Corinna C, Henssen Anton G AG, Stephan Harald H, Schröder Christopher C, Heukamp Lukas L, Engesser Anne A, Kahlert Yvonne Y, Theissen Jessica J, Hero Barbara B, Roels Frederik F, Altmüller Janine J, Nürnberg Peter P, Astrahantseff Kathy K, Gloeckner Christian C, De Preter Katleen K, Plass Christoph C, Lee Sangkyun S, Lode Holger N HN, Henrich Kai-Oliver KO, Gartlgruber Moritz M, Speleman Frank F, Schmezer Peter P, Westermann Frank F, Rahmann Sven S, Fischer Matthias M, Eggert Angelika A, Schulte Johannes H JHVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASP[M]Neuroblastoma NOS (morphologic abnormality), Relapse, Neuroblastoma (Schwannian Stroma-Poor), relapse, neuroblastoma, (Neuroblastoma NOS) or (sympathicoblastoma), Recrudescence, Neuroblastomas, Neuroblastoma, Recrudescences, [M]Neuroblastoma NOS, neuroblastoma NOS (morphologic abnormality)., Recurrences, Central neuroblastoma, NOS, NB, Relapses, NB - Neuroblastoma, neuroblastoma (morphologic abnormality), SympathicoblastomaRelapse, Malignant Neoplasm, Data Set, Malignancy, Neuroblastomas, Neuroblastoma, Recrudescences, Neoplasms, Recurrences, Benign Neoplasm, Benign Neoplasms, patient, Cancers, Tumor, Recurrences., Malignant, Client, Malignant Neoplasms, Neoplasias, relapse, Benign, Patient, Recrudescence, Clients, Neoplasm, Malignancies, NB, Relapses, other neoplasm, Neoplasia, Cancer, TumorsYAP65, Antemortem Diagnosis, Materials, tumor suppressor, Activity, determination, pars sympathica divisionis autonomici systematis nervosi, selection process, YY1AP, Neuroblastoma., Yap65, c-rasHa, Visible Light, sympathetic part of autonomic division of nervous system, DNA Methylations, Tumor, Diagnosis, Mutations, dmTAF[[II]]230, relapse, cell cycle regulator, OTTMUSG00000022087, ras, Nervous Systems, symptoms, Whole Transcriptome, Transcriptome Sequencing, Relapses, C130080N23Rik, C-K-RAS, Non Polyadenylated, k-ras, rask2, Progression, increased, DNA methylation maintenance, Yap, YAP, TFIID TAF250, H-RASIDX, cel, Complete Exome Sequencing, Polyadenylated Messenger, Recurrences, Whole Transcriptome Sequencing, hypoplasia, chromatid, DNA methylation, Sympathetic Nervous Systems, genetic, reaction, TNFSF14, N-RAS, yap, Exacerbation, 1200017A24Rik, Malignancies, Diagnose, single organism signaling, Tumors, Relapse, screening, dTAF[[II]]230, Radiation, Polyadenylated, Ki-ras, UNQ391/PRO726, frequency, Exome, Disease Exacerbation, familial, TAF200, Light, TAFII-250, TAF250/230, Diagnoses, PTP36, TAFII250, Benign, Postmortem, Screenings, LIGHT, Recrudescence, Examinations and Diagnoses, HCCA1, p21, HCCA2, Genetic Materials, Postmortem Diagnosis, Genetic Material, Polyadenylated Messenger RNA, Visible Radiations, Diagnoses and Examination, AW060752, YAP2, Complete Transcriptome, Postmortem Diagnoses, Visible Radiation, Non Polyadenylated mRNA, protein_coding_transcript, HVEML, Neuroblastomas, c-Ha-ras, System, Sympathetic, CHDS5, Hras-1, signs, Benign Neoplasms, CG17603, TAF[[II]], surveillance, morbidity, Non-Polyadenylated mRNA, 4930532L22Rik, Malignant Neoplasms, p21ras, Sympathetic Nervous, array CGH, Patient, Chromosome, HRAS1, RASK2, Taf250, c-H-ras, Material, SR3-5, Whole Exome Sequencing, H-Ras, Cistron, inherited genetic, DNA, MRD2, Transcriptome Sequencings, Poly(A) RNA, Harvey-ras, Methylation, accessory, TAF230, Hras1, KI-RAS, PEZ, d230, TRAD, DmelCG4005, Complete Exome, Neoplasms, Kras2, NS3, Benign Neoplasm, H-ras, Gene, dTAFII250, HEL-205, Malignant, hras1, EfW1, supernumerary, DUET, Ly113, reduced, dmTAF1, Messenger, Taf230, AI461977, Mass, Clinical Progression, Screening, Kras-2, tiny, Antemortem, C-BAS/HAS, Ha-ras, KRAS2, KRAS1, TAF250, p21B, ARHGEF24, Nervous System, WES, Taf200, Complete, Exome Sequencings, dTAF[[II]]250, Clinical, pattern, Genetic, 5530402J05Rik, Malignancy, occurrence, Recrudescences, distribution, cell, RASH1, K-RAS4B, K-RAS4A, prevalence, messenger RNA, Taf1p, Diagnoses and Examinations, Visible, Sequencing, Neoplasias, C030018G21Rik, dTAF250, template RNA, Whole Exome, C-BAS|HAS, Clinical Course, Clients, Whole, heterogeneity, RIGB, TR2, Yki, YKI, TAF, constitutitional genetic, Methylations, Yorkie, incidence, Cancer, small, Antemortem Diagnoses, RNA, Disease, COB1, TAF[[II]]250, findings, Malignant Neoplasm, Complete Exome Sequencings, CHD5, K-RAS2B, K-RAS2A, Messenger RNA, l(3)84Ab, K-ras, BG:DS00004.13, rash1, c-Ki-ras, Cistrons, CD258, Client, Examination and Diagnoses, Cell, dTAF230, Exome Sequencing, prophase chromosome, A130095G14Rik, MT, Mass Screenings, CTLO, Poly(A)+ mRNA, p230, Systems, chemical analysis, Neoplasm, CG4005, INSDC_feature:mRNA, TAF[[II]]250/230, TFIID, NB, K-Ras, K-RAS, Polyadenylated RNA, methylation, CHD-5, Chd5, AI929937, CHD-6, outbreaks, C-HA-RAS1, ZIR8, Radiations, Taf[[II]]250, HAMSV, Poly(A)+ RNA, NS, Complete Transcriptome Sequencing, TAF[[II]]230, mRNA, Poly(A) Tail, underdeveloped, B230399N07Rik, Neuroblastoma, HAPIP, HVEM-L, increased number, interphase chromosome, Photoradiation, Non-Polyadenylated, patient, TAF[II]250, Cancers, AI325207, endemics, LTg, DUO, present in greater numbers in organism, C-H-RAS, DmelCG17603, Photoradiations, signalling process, kras, CFC2, epidemics, assay, Polyadenylated mRNA, hereditary, General activity, Neoplasia, 5830472H07Rik, TAF1falseena-DATASET-UKEssen-09-09-2015-10:54:33:815-144 - samplesIn this dataset, 16 trios- primary tumor, relapse and corresponding normals- for patients with neuroblastoma are provided. For one patient, more than one relapse was available for the analyses.2017-07-26 15:39:26EGAD00001001607960626121086EGAC00001000373EGAS00001001387