{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001002705"],"host":["EGA"],"description":["EGA study EGAS00001002705"],"dataset_title":["Variant calling analysis of cfDNA whole exome sequencing in neuroblastoma"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["Therapy, dTAF[[II]]230, TAF[[II]]250, d230, Complete Exome Sequencings, DNS, insensitive, (Deoxyribonucleotide)n, Complete Exome, DNAn+1, Neuroblastoma., Exome, TAF200, l(3)84Ab, dTAFII250, BG:DS00004.13, Double-Stranded, TAFII-250, TAF250/230, EfW1, Cell, Deoxyribonucleic acids, dTAF230, (Deoxyribonucleotide)n+m, dmTAF[[II]]230, Exome Sequencing, TAFII250, Deoxyribonucleic Acid, dmTAF1, Taf230, p230, TAF[[II]]250/230, TFIID, Whole Transcriptome, Transcriptome Sequencing, NB, ds-DNA, desoxyribose nucleic acid, TAF250, Taf[[II]]250, treatment, WES, Complete Transcriptome, Taf200, thymus nucleic acid, Complete, Complete Transcriptome Sequencing, Exome Sequencings, dTAF[[II]]250, TAF[[II]]230, TFIID TAF250, resistant, Neuroblastomas, cel, cell, Complete Exome Sequencing, Whole Transcriptome Sequencing, Double Stranded, Taf1p, TAF[II]250, Deoxyribonucleic acid, CG17603, TAF[[II]], free, Treatments, Sequencing, dTAF250, Whole Exome, DmelCG17603, Taf250, Therapeutic, SR3-5, Whole, ds DNA, heterogeneity, Whole Exome Sequencing, disease management, Desoxyribonukleinsaeure, Therapies, Treatment, Double-Stranded DNA, (Deoxyribonucleotide)m, DNA, deoxyribonucleic acids, DNAn, TAF, Transcriptome Sequencings, TAF230, TAF1"],"description_synonyms":["DmErk, extracellular signal-regulated kinase activity, pp44mapk, Materials, growth and development, Tumor, Diagnosis, Prp4 protein kinase activity, Mutations, cAMP signaling, LeMPK3, Method, ATP-protein transphosphorylase activity, p44mpk, ATP:protein phosphotransferase (non-specific) activity, symptoms, Dp38, Whole Transcriptome, Transcriptome Sequencing, SAPK2, SEM, Sem, treatment, MAP-k, Cell Division Cycles, thymus nucleic acid, protein kinase A signalling cascade, D15F32S1h, Biopsies, pp42, Dsor2, procedures, Evolution, sem, Ligase, NOR-1, s, Homo sapiens disease, Nucleotide, Diagnose, Tumors, ERK-A, p82 kinase activity, screening, dpERK, dpErk, CHN, Exome, betaIIPKC, protein kinase A signaling, DmMAPK, PMK-2, Procedure, dp-ERK, PMK-1, CEP52, Diagnoses, PMK-3, Wee-kinase activity, Benign, Postmortem, Recrudescence, pMAPK, pMapK, desoxyribose nucleic acid, nucleotides, Ubiq, Complete Transcriptome, DmERKA, rl/MAPK, follow up, signs, non-specific serine/threonine protein kinase activity, Benign Neoplasms, l(2)41Ac, Methodological, Malignant Neoplasms, CT34260, dpERk, CG11734, Material, serine-specific protein kinase activity, ds DNA, Whole Exome Sequencing, SAPK, HIPK2, cytidine 3', DNA, other neoplasm, Wee 1-like kinase activity, DNS, glycogen synthase A kinase activity, (Deoxyribonucleotide)n, Neoplasms, glycogen synthase kinase 3 activity, number, 12559, ATP Dependent Proteolysis Factor 1, protein-containing complex, phosphorylase b kinase kinase activity, EK2-1, Human, Deoxyribonucleic Acid, Gene Products, Screening, disease or disorder, Antemortem, ribosomal protein S6 kinase II activity, rjs, Technique, Erk, ERK, PRKM1, Cycles, PRKM2, protein-serine kinase activity, Complete, Exome Sequencings, Genetic Heterogeneities, Recrudescences, STK32, Cell Division Cycle, cell-division cycle, Double Stranded, D7H15F32S1, Deoxyribonucleic acid, Diagnoses and Examinations, Sequencing, erk, Neoplasias, Study, 40S ribosomal protein S27a, Whole Exome, protein-cysteine kinase activity, Whole, Hpr kinase activity, rll, (Deoxyribonucleotide)m, STK26, p38-2, protein tagging activity, myelin basic protein kinase activity, Cancer, Antemortem Diagnoses, findings, Malignant Neoplasm, Complete Exome Sequencings, DNAn+1, protein kinase A signaling cascade, Proteins, disorders, stress-activated kinase activity, MAP-2 kinase activity, MRT38, protein serine kinase activity, Cell, protein phosphokinase activity, Exome Sequencing, Ubiquitin A-52 residue ribosomal protein fusion product 1, PKA, native protein, PKC, Ubiquitin-related 2, stress-activated protein kinase activity, chemical analysis, mapk2, mapk1, Neoplasm, condition, NB, background, protein kinase p58 activity, serine/threonine protein kinase activity, covalent modifier, CG12559, dpERK1, postnatal growth, Heterogeneities, Cancers, dsk1, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, plan specification, Gene Proteins, dpMAPK, 60S ribosomal protein L40, ligase, Desoxyribonukleinsaeure, DmelCG11734, Ubiquitin-related, PKA signaling cascade, protein serine-threonine kinase activity, Neoplasia, SAP kinase activity, glycogen synthase kinase activity, Antemortem Diagnosis, protein kinase A activity, insensitive, single-organism developmental process, determination, Mpk2, postnatal development, p42mapk, CSMF, protein, SR2-1, Liquid Biopsies, Techniques, relapse, Clonal, diseases, kinase-related transforming protein, diseases and disorders, mitogen-activated protein kinase activity, Relapses, protein aggregate, mpk1, human disease, Erk/Map kinase, High Mobility Protein 20, Complete Exome Sequencing, Whole Transcriptome Sequencing, Recurrences, DERK-A, Ubiquitin-related 1, E(sina)7, Rl, free, Raf kinase activity, APF-1, MP kinase activity, serine kinase activity, DERK, Methodological Studies, atypical protein kinase C activity, Cell Cycles, disease management, Therapies, MBP kinase II activity, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, Malignancies, Double-Stranded DNA, dERK, Biopsy, deoxyribonucleic acids, DNAn, time point, Therapy, Relapse, MAP kinase 2 activity, Mapk, D7H15F37S1, Erk1, ERK1, ERK2, mapk1a, Double-Stranded, results, Division Cycles, mKIAA0393, (Deoxyribonucleotide)n+m, M phase-specific cdc2 kinase activity, Screenings, mapk1b, MapK, MAPK, Examinations and Diagnoses, Diseases, Genetic Materials, overlap, Postmortem Diagnosis, serine protein kinase activity, erk2, Genetic Material, mapk, Ubiquitin, Diagnoses and Examination, SHEP1, ERKa, phosphorylase B kinase kinase activity, Postmortem Diagnoses, D15F37S1, BcDNA:RE08694, protein glutamyl kinase activity, resistant, Neuroblastomas, Division Cycle, l(2R)EMS45-39, Heterogeneity, DmelCG12559, Human Ubiquitin, common, p38, Methodological Study, Treatments, DpErk, DpERK, ErkA, disease, ERKA, hydroxyalkyl-protein kinase activity, WEE1Hu, Patient, epsilon PKC, Liquid, Cistron, Diagnoses., p528, Transcriptome Sequencings, pERK, other disease, ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, Procedures, GroupII, Complete Exome, Benign Neoplasm, Gene, Synthetases, Ubiquitin carboxyl extension protein 80, Malignant, presence, Deoxyribonucleic acids, method, Genetic heterogeneity, method used in an experiment, Cycle, Studies, Mass, serine(threonine) protein kinase activity, HMG-20, T-antigen kinase activity, galactosyltransferase-associated kinase activity, study, Somatic, WES, Genetic, Malignancy, AI573420, xp42, Cell Division, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, non-neoplastic, protein kinase (phosphorylating) activity, Raf-1, Clients, ubiquitin, disorder, DmERK-A, PKA signaling, jdf2, casein kinase (phosphorylating) activity, NOR1, ert1, Nor1, protein complex, prkm2, prkm1, CT39192, medical condition, Cistrons, Client, Somatic Evolution, Examination and Diagnoses, p38delta, development, count in organism, twitchin kinase activity, Mass Screenings, AP50 kinase activity, Protein, MBP kinase I activity, Synthetase, techniques, ds-DNA, ATP-Dependent Proteolysis Factor 1, Xp42, threonine-specific protein kinase activity, Complete Transcriptome Sequencing, distinct, MINOR, Neuroblastoma, mitogen activated kinase activity, Su(Raf)2B, EY2-2, introduction, Protein Gene Products, D-ERK, Therapeutic, cardinality, Treatment, TEC, assay, growth, Minor, methodology, MAP kinase 1 activity, A-kinase activity"],"additional_accession":[]},"is_claimable":false,"name":"Whole exome sequencing of cell-free DNA reveals temporo-spatial heterogeneity and identifies treatment-resistant clones in neuroblastoma","description":"Background: Neuroblastoma (NB) displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. Patients and Methods: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 NB patients. Results: WES of the primary tumor and cfDNA at diagnosis showed overlap of Single Nucleotide Variants (SNVs) and Copy Number Alterations (CNAs), with 41% and 93% of all detected alterations common to the primary NB and cfDNA. CfDNA WES at a second time point indicated a mean of 22 new SNVs for patients with progressive disease. Relapse-specific alterations included genes of the MAPK pathway and targeted the protein kinase A signaling pathway. Deep coverage target sequencing of intermediate timepoints during treatment and follow-up identified distinct subclones. For 17 seemingly relapse-specific SNVs detected by sequencing detected these alterations in minor subclones, with relapse-emerging SNVs targeting genes of neuritogenesis and cell cycle. Furthermore a persisting, resistant clone with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2. Conclusion: Modelisation of mutated allele fractions in cfDNA indicated distinct patterns of clonal evolution, with either a minor, treatment-resistant clone expanding to a major clone at relapse, or minor clones collaborating towards tumor progression. Identification of treatment-resistant clones will enable development of more efficient treatment strategies.cfDNA WES at relapse but not tumor or cfDNA WES at diagnosis, deep coverage target.","dates":{"updated":"2019-10-01 17:00:30"},"accession":"EGAS00001002705","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001003803","EGAC00001000319"]}}