EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001007650EGAEGA study EGAS00001007650scDNA-seq for 'Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma'Amplicon Sequencing for 'Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastoma'WES data for Early evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastomarestrictedEGAlod, Therapy, DmelCG2684, Pharmacotherapy, Neuroblastomas, chemotherapy, Neuroblastoma., pharmacotherapy, Pharmacotherapies, NTef2, Lds, early, Fs(3)Sz11, Chemotherapies, Drug, Horka, CG2684, Therapies, Fs(3)Horka, Chemotherapy, pharmacologic therapy, NB, DmF2, Fs(3)Hor, Drug Therapiesother disease, Antemortem Diagnosis, l(3)e77A1, Heterograft, chemotherapy, Neoplasms, Benign Neoplasm, AT V1, microcephaly with normal intelligence immunodeficiency and lymphoreticular malignancies, pharmacotherapy, Pharmacotherapies, TRANSPL HETEROL, Tumor, Transplantations, Foundation, Malignant, with normal intelligence, Diagnosis, NBS, Nbs, Chemotherapies, heterologous transplantation, sparse hair and mental retardation, Mutations, diseases, CG9063, Mass, symptoms, Screening, disease or disorder, diseases and disorders, Antemortem, 6754, Cell Culture, Drug Therapies, NBs, nbs, treatment, NCBRS, sparse hair and intellectual disability, human disease, Complete, Whole Genome, l(3)67BDr, Malignancy, Immunodeficiency - microcephaly - chromosomal instability, Nonsyndromal microcephaly autosomal recessive with normal intelligence, variant 1, l(3)67BDp, Complete Genome Sequencing, Heterografts, NDPK-A, Diagnoses and Examinations, immunodeficiency, NDPKA, BcDNA:GH03694, GAAD, Sequencing, Cell Culture Technique, non-neoplastic, Neoplasias, NM23, DmelCG6754, Xenotransplantations, P95, Whole, disease management, Therapies, disorder, Homo sapiens disease, Malignancies, Nonsyndromal microcephaly, Microcephaly - immunodeficiency - lymphoreticuloma, microcephaly immunodeficiency lymphoreticuloma, Seemanova syndrome type 2, DmelCG9063, Diagnose, Heterologous, Cancer, Tumors, Therapy, Antemortem Diagnoses, screening, ATV, Culture Techniques, findings, Malignant Neoplasm, disorders, Genome Sequencing, medical condition, Examination and Diagnoses, Cell, Diagnoses, disease management., MT, Benign, Postmortem, Screenings, XENOTRANSPL, Complete Genome, NDKA, Berlin breakage syndrome, Mass Screenings, Examinations and Diagnoses, Diseases, Neoplasm, Chemotherapy, condition, Ataxia-telangiectasia, NB, Postmortem Diagnosis, Heterologous Transplantations, microcephaly with normal intelligence, autosomal recessive, Culture Technique, Diagnoses and Examination, Xenograft, Postmortem Diagnoses, Xenotransplantation, Pharmacotherapy, Neuroblastomas, Transplantation, Neuroblastoma, NICOLAIDES-Baraitser syndrome, AT-V2, AWD, BcDNAGH03694, AT-V1, CG6754, signs, Benign Neoplasms, ataxia-telangiectasia variant V1, HETEROL TRANSPL, NBS1, Nbs1, Cancers, ataxia-telangiectasia variant V2, Xenografts, Treatments, 3L6, Malignant Neoplasms, Drug, microcephaly, and chromosomal instability, nbs1, Seemanova syndrome 2, disease, Dnbs1, Therapeutic, rich, Cell Cultures, Treatment, pharmacologic therapy, NM23-H1, other neoplasm, Neoplasia, and lymphoreticular malignanciesfalseEarly evolutionary branching across spatial domains predisposes to clonal replacement under chemotherapy in neuroblastomaNeuroblastoma (NB) is one of the most lethal childhood cancers due its propensity to treatment resistance. By spatial mapping of subclone geographies before and after chemotherapy across 89 tumor regions from 12 NBs, we find that densely packed territories of closely related subclones present at diagnosis are replaced under effective treatment by islands of distantly related survivor subclones, originating from a different most recent ancestor compared to lineages dominating before treatment. Conversely, in tumors that progressed under treatment, ancestors of subclones dominating later in disease are present already at diagnosis. Chemotherapy treated xenografts and cell culture models replicates these two contrasting scenarios and shows branching evolution to be a constant feature of proliferating NB cells. Phylogenies based on whole genome sequencing of 505 individual NB cells indicate that a rich repertoire of parallel subclones, emerges already with the first oncogenic mutations and lays the foundation for clonal replacement under treatment.2024-10-01 12:44:04EGAS000010076509606EGAD00001015012EGAD00001015414EGAD00001015413EGAC00001000534