EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001007019EGAEGA study EGAS00001007019Neuroblastoma deep-sequencing dataset part2EGArestrictedNB, heterogeneity., Neuroblastomas, Neuroblastomal(1)G0134, chromosomal crossover, DmelCG6146, neuroblastoma, Activity, heterogeneity., determination, Nmyc, Neoplasms, Central neuroblastoma, ODED, Benign Neoplasm, mycna, mycnb, Tumor, TOP1ALPHA, Malignant, protrusion, topo I, Relative, mycn, Recombinations, Topo I, resilient, tough, NMYC, CG18144, MGOUN 1, nmyc, strong, l(1)G0278, AI467334, Malignancy, Genomes, top1, DNA topoisomerase 1 beta, Top-1, Homologous, HAND, dHand, bHLHa28, Nmyc1, chromatid, N-myc, topoI, Nmuc1, neuroblastoma (morphologic abnormality), TOPOISOMERASE 1, Dhand, foot, hand, [M]Neuroblastoma NOS (morphologic abnormality), Neoplasias, l(1)G0201, MODED, hand-C, XN-myc, Clients, [M]Neuroblastoma NOS, heterogeneity, dHAND, Malignancies, NB - Neuroblastoma, D130064I21Rik, bHLHe37, associated, XNmyc, TopoI, Cancer, Tumors, forefoot of quadruped, topi, Neuroblastoma (Schwannian Stroma-Poor), anatomical protrusion, Malignant Neoplasm, Homologous Recombinations, MTE17.2, TopI, TOPI, Client, Sympathicoblastoma, MTE17.1, prophase chromosome, Benign, paw, l(1)G0229, fore-paw, MTE17_1, MTE17_2, Relative Risks, c-nmyc, chemical analysis, Neoplasm, NOS, dTopoI, NB, CG6146, forefeet, TOP1, Relative Risk, xN-myc1, Recombination, MAK17, TOP1BETA, Risk, Neuroblastomas, Neuroblastoma, interphase chromosome, reciprocal DNA recombination, DmelCG18144, Risks, Benign Neoplasms, Cancers, l(1)top1, Malignant Neoplasms, neuroblastoma NOS (morphologic abnormality), Nmyc-1, Hands, (Neuroblastoma NOS) or (sympathicoblastoma), Patient, Chromosome, spine, fore foot, DNA topoisomerase I alpha, fore paw, forepaw, assay, Ab2-086, MGO1, other neoplasm, forefoot, MAK1, General activity, NeoplasiafalseNeuroblastoma heterogeneityNeuroblastoma is a pediatric solid tumor characterized by strong clinical heterogeneity. Although certain complex genomic alterations, such as extrachromosomal DNA amplifications (ecDNA), are associated with adverse outcomes and have been recurrently detected in neuroblastomas, the mutational processes involved in their generation remain largely unclear. By examining the topography of complex rearrangements along with mutational signatures derived from all variant classes, we identify previously unrecognized co-occurring mutational footprints, which we termed mutational scenarios. We demonstrate that clinical neuroblastoma heterogeneity is linked to differences in the processes driving these mutational scenarios. Whereas high-risk MYCN-amplified neuroblastoma genomes were characterized by signs of replication slippage and stress, homologous recombination-associated signatures defined high-risk non-MYCN-amplified patients. Non-high-risk neuroblastomas, on the other hand, were marked by footprints of chromosome missegregation and TOP1 mutational activity. This analysis provides a systematic perspective on the repertoire of mutational patterns that contribute to clinical neuroblastoma heterogeneity.2023-05-16 11:29:43EGAS000010070199606EGAD00001010063EGAC00001003104