{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Cancer Genomics"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001006027"],"host":["EGA"],"description":["EGA study EGAS00001006027"],"dataset_title":["Berlin Neuroblastoma Patient Genomic Data from Targeted Sequencing"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["TARGET, Destination, Targeting, ctdDNA, Amenable, target_lesion, Target Lesion Identification, determination, Index, Neuroblastomas, Biological Detection Test, ctDNA, Neuroblastoma., Target, Targeted, Early Recurrence, Circulating Tumor-Derived DNA, DETECTION, Client, Patient, Circulating Tumor DNA, Clients, chemical analysis, Cell-Free Circulating Tumor DNA, target lesion, Suitable, Early Relapse, NB, assay, Detected, Detection"],"description_synonyms":["Experimental Designs, Disorders, Adjustments, Date of Diagnosis, PROSPECTIVE, Design, Error Sources, NCI Thesaurus Concept, cfDNA, Tumor, Tumour, Diagnosis, Mutations, dmTAF[[II]]230, Personal, Compared, cerebral spinal fluid, mili, Method, ALK NP_004295.2:p.R1275Q, Muscle-Specific, Correlated, symptoms, ALK Tyrosine Kinase Receptor Arg1275Gln, correlation, Prospective Tissue Collection, 2 Phospho D Glycerate Hydrolase, treatment, Correlation, Detectable, Fresh Frozen, thymus nucleic acid, Biopsies, TFIID TAF250, cel, Molecular, INTRATUMOR, Matched Group, Metathesaurus Concept, Matched, Comparison, Nmyc1, Enolase, Social, replicate, Residual Disease, high frequency, Reporting, Non-Neuronal, ALK R1275Q, Muscle Specific Enolase, Social Power, ALK p.F1174L, plasma, Diagnose, Power, Data Reporting, Tumors, screening, dTAF[[II]]230, Apply, Research Technic, Diagnosed, Research Methodology, ALK NP_004295.2:p.F1174L, TAF200, Early Recurrence, ALK p.R1275Q, Molecular Target, DETECTION, Collected, Research Proposal, prospective, Diagnoses, Cell Free Ribonucleic Acid, Electrical Current, disease_type, Experimental, Postmortem, Benign, Marker, 2-Phospho-D-glycerate hydro-lyase, CURRENT, High-Risk Neuroblastoma, Dx, Technics, Circulating Nucleic Acids, Cell-Free Deoxyribonucleic Acid, Problem Formulation, NP_004295.2:p.R1275Q, desoxyribose nucleic acid, CD246 Antigen Arg1275Gln, xN-myc1, Acid, portion of blood plasma, Non-Neoplastic, Relational and Item-Specific Encoding Task, Residual, Biological Detection Test, Cell Free Nucleic Acids, Nucleic Acids, signs, Benign Neoplasms, Cerebro, surveillance, Malignant Neoplasms, Formulations, Non-Neuronal Enolase, blood plasm, Prospective Collection, Taf250, monitor, Info, Diseases and Disorders, ds DNA, Acids, DNA, Detected, other neoplasm, Neuron-Specific Enolase, Data Adjustments, TAF230, Fresh, Psychological Power, NBLST3, Clinical Batch, DNS, Fresh Frozen Plasma, (Deoxyribonucleotide)n, Cell-Free Deoxyribonucleic, Residual Minimal Diseases, Nmyc, Molecular Marker, Neoplasms, signature molecule, Matched Groups, ODED, Prospective, Circulating Cell-Free Nucleic Acid, Adjustment, Collected Value, Deoxyribonucleic Acid, isolation, alpha Enolase, Cell-Free RNA, Sources, NMYC, Tcrz, Screening, Cerebro Spinal, Antemortem, nmyc, Technique, CD246 Antigen R1275Q, Higher, Application, Pediatric, ALK p.Arg1275Gln, dTAF[[II]]250, Clinical, Supply, Diagnostic, CNS, occurrence, cell, prevalence, Target, Double Stranded, Tumor Tissue, Deoxyribonucleic acid, Diagnoses and Examinations, Nmuc1, Cell-Free Ribonucleic, Monitoring, DETECT, Research Strategy, Neoplasias, dTAF250, Hydro-Lyase, Supplied, Routine, NP_004295.2:p.Phe1174Leu, I-TUMOR, (Deoxyribonucleotide)m, bHLHe37, Anaplastic Lymphoma Kinase R1275Q, XNmyc, Cancer, ALK, ALK Arg1275Gln, Antemortem Diagnoses, RNA, findings, Malignant Neoplasm, DAlk53, Longitudinal Study, longitudinal study, Minimal Disease, DNAn+1, Neuron Specific Enolase, ddPCR, Matching, Fluids, 2-phospho-D-glycerate hydro-lyase, copies, ALK NP_004295.2:p.Phe1174Leu, BG:DS00004.13, spinal fluid, Cell, Neuron-Specific, Spinal Fluid, Collecting, dTAF230, Circulating RNA, Concept, Research Strategies, Frozen Plasmas, Spinal Fluids, Fluid, tumor-derived, diagnosis, Have, chemical analysis, cerebrospinal axis, Neoplasm, TAF[[II]]250/230, condition, clinical, Replicate, beta Enolase, Approach, Collection, Option, outbreaks, Cell-Free DNA, Destination, CD246 Antigen F1174L, Taf[[II]]250, Relational and Item-Specific Encoding (RiSE), Intratumor Route of Administration, Body Fluid, Treated, Information, Match, disease term, Anaplastic Lymphoma Kinase Arg1275Gln, Neural enolase, Upon Relapse, Research Designs, Residual Neoplasms, Residual Minimal Disease, Research Technics, Ribonucleic Acid, CSF, Cancers, Childhood, Body, High, Data Adjustment, Residual Cancers, At Relapse, Error, Specific, Power (Psychology), Desoxyribonukleinsaeure, epidemics, Hydratase, disease_term, Strategy, Isolation, ALK F1174L, CD246, Neoplasia, Research Technique, Biological Markers, Antemortem Diagnosis, Problem Formulations, Residual Tumors, insensitive, determination, Blood, clinical data, Recurrent Neuroblastoma, mycna, mycnb, molecular marker, Circulating, Technic, Highly, Circulating DNA, disease type, Techniques, Guide Device, monitoring, Cell-Free, Nervous System-Specific Enolase, liquor cerebrospinalis, Cell-Free Nucleic Acid, Non Neuronal Enolase, {Copies}, Biomarkers, Cell Free Nucleic Acid, Detection, Nervous System-Specific, Experimental Design, High Risk Neuroblastoma, Psychological, Group, CD246 Antigen Phe1174Leu, Fresh Frozen Plasmas, Targeting, cirDNA, Identification, Provide, Signature Molecule, Designs, Groups, Copies, experimental design, N-myc, free, gamma-Enolase, Had, Other Disease, XN-myc, Residual Tumour, 2-Phospho-D-Glycerate, disease management, Therapies, Research Techniques, Double-Stranded DNA, Malignancies, deoxyribonucleic acids, Intratumor, DNAn, Has, Therapy, Cerebro Spinal Fluid, 2-Phospho-D-Glycerate Hydro-Lyase, Frozen Plasma, frequency, TUMOR TISSUE, pediatric, DROPLET DIGITAL PCR, Research Proposals, Psychological Powers, Double-Stranded, TAFII-250, TAF250/230, Plasmas, ALK Tyrosine Kinase Receptor R1275Q, results, (Deoxyribonucleotide)n+m, Cerebro Spinal Fluids, DAlk, TAFII250, Screenings, Examinations and Diagnoses, Diseases, dALK, Minimal Residual Diseases, Postmortem Diagnosis, Problem, 2 Phosphoglycerate Dehydratase, Clinical Data, Residual Cancer, Options, Diagnoses and Examination, Guide, Postmortem Diagnoses, concept, resistant, Circulating Cell Free Nucleic Acids, NP_004295.2:p.F1174L, RiSE, Droplet Digital PCR, Anaplastic Lymphoma Kinase F1174L, 2-Phosphoglycerate Dehydratase, CG17603, TAF[[II]], Muscle-Specific Enolase, morbidity, Treatments, Identified, disease, Terminology Concept, Residual Tumor, Patient, Purpose, SR3-5, ALK Tyrosine Kinase Receptor Phe1174Leu, Powers, Administered Component Concept, Provided, d230, gamma Enolase, Professional Power, Circulating Cell Free Nucleic Acid, Benign Neoplasm, Correlative, dTAFII250, Isolated, Scoring Method, Dehydratase, Compare, EfW1, Malignant, Deoxyribonucleic acids, Cerebrospinal, NSE, Anaplastic Lymphoma Kinase Phe1174Leu, Residual Neoplasm, mycn, NP_004295.2:p.Arg1275Gln, dmTAF1, Scoring Methods, Taf230, Minimal, CG8250, Mass, Cell Free DNA, Intratumoral Route of Administration, Phosphopyruvate, Current, 4.2.1.11, TAF250, Biomarker, Methodology, Taf200, Cell Free Deoxyribonucleic Acid, Blood Plasma, Scoring, Malignancy, DIAG, Research, Proposals, Biological Marker, Taf1p, Treatments., Circulating Cell-Free Nucleic Acids, Nervous System Specific Enolase, MODED, Minimal Residual Disease, Relational and Item-Specific Encoding, COLLECTING, beta-Enolase, ALK Tyrosine Kinase Receptor F1174L, Clients, Disorder, Blood Plasmas, ALK p.Phe1174Leu, heterogeneity, Error Source, Conceptual, disorder, liquid, biological marker, Strategies, TAF, Dosing Days to Detection, incidence, DmelCG8250, 2-Phospho-D-Glycerate Hydrolase, date of diagnosis, Possess, Disease, TAF[[II]]250, neuraxis, 2-Phosphoglycerate, Residual Tumours, Tumor-Derived, date_of_diagnosis, Targeted, l(3)84Ab, Cerebrospinal Fluids, Formulation, Client, Examination and Diagnoses, DIAGNOSIS, ALK NP_004295.2:p.Arg1275Gln, Clinical Lot, Circulating Nucleic Acid, Mass Screenings, p230, Nucleic Acid, biomarker, Applied, c-nmyc, Disease or Disorder, ALK Phe1174Leu, TFIID, Professional, Copy, marker, ds-DNA, Cell Free RNA, Relapsed Neuroblastoma, Proposal, Methods, Tumor Sample, Plasma, Enolase 2, purpose, TAF[[II]]230, frequent, Source, alpha-Enolase, Intratumoral use, portion of plasma, cirRNA, TAF[II]250, Neuraxis, endemics, Healthy, Nmyc-1, cfRNA, Specified, Personal Power, Circulating Nucleic, DmelCG17603, Treating, Therapeutic, Cell-Free Ribonucleic Acid, Data, Nervous, Treatment, 2 Phospho D Glycerate Hydro Lyase, Early Relapse, assay, Total, Duplicate, System-Specific Enolase, Enolase 3, TAF1, Neuron-specific enolase"],"additional_accession":[]},"is_claimable":false,"name":"Targeted analysis of cell-free circulating tumor DNA is suitable for early relapse and actionable target detection in patients with neuroblastoma","description":"Purpose: Treating refractory or relapsed neuroblastoma remains challenging. Monitoring body fluids for tumor-derived molecular information indicating minimal residual disease supports more frequent diagnostic surveillance and may have the power to detect resistant subclones before they give rise to relapses. If actionable targets are identified from liquid biopsies, targeted treatment options can be considered earlier.\nExperimental design: Droplet digital PCR assays assessing MYCN and ALK copy numbers and allelic frequencies of ALK p.F1174L and ALK p.R1275Q mutations were applied to longitudinally collected liquid biopsies and matched tumor tissue samples from 31 patients with high-risk neuroblastoma. Total cell-free DNA (cfDNA) levels and marker detection were compared with data from routine clinical diagnostics.\nResults: Total cfDNA concentrations in blood plasma from patients with high-risk neuroblastoma were higher than in healthy controls and consistently correlated with neuron-specific enolase levels and lactate dehydrogenase activity but not with 123I-meta-iodobenzylguanidine scores at relapse diagnosis. Targeted cfDNA diagnostics proved superior for early relapse detection to all current diagnostics in two patients. Marker analysis in cfDNA indicated intratumor heterogeneity for cell clones harboring MYCN amplifications and druggable ALK alterations that were not detectable in matched tumor tissue samples in 17 patients from our cohort. Proof-of-concept is provided for molecular target detection in cerebrospinal fluid from patients with isolated CNS relapses.\nConclusions: Tumor-specific alterations can be identified and monitored during disease course in liquid biopsies from pediatric patients with high-risk neuroblastoma. This approach to cfDNA surveillance warrants further prospective validation and exploitation for diagnostic purposes and to guide therapeutic decisions.","dates":{"updated":"2022-02-14 12:07:17"},"accession":"EGAS00001006027","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001008564","EGAC00001002532"]}}