EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001003385EGAEGA study EGAS00001003385Ewing's Sarcoma Whole Genome SequencingEGArestrictedEwing's family localized tumor, Ewing's Family of Tumors, localized Ewing's sarcoma/peripheral primitive neuroectodermal tumor, sarcoma, peripheral neuroectodermal tumor (morphologic abnormality), Ewing's sarcoma, Ewing sarcoma family of tumors, Genome Sequencing, Tumor, Ewing Family of Tumors, EFTs, peripheral, PNET of Thoracopulmonary region, localized peripheral primitive neuroectodermal tumor, PNET of Thoracopulmonary Region, Complete Genome, Ewing's Sarcoma, Ewing's tumour, peripheral neuroectodermal tumor (disorder), ES, Tumors of the Ewing's Family, Ewing sarcoma, Tumors of Ewing's Family, Complete, Whole Genome, Ewings sarcoma-primitive neuroectodermal tumor, neuroepithelioma, peripheral neuroepithelioma (disorder), Ewings sarcoma, Complete Genome Sequencing, Ewing Tumor, Ewing, Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor, 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tumour, thymus nucleic acid, human disease, DmelCG2684, Genomes, Moods, Tissue, CG3606, localized Ewing's tumor, NTef2, Signatures, Ewing's Family of Tumours, Sarcoma, Malignant neoplasm of soft tissue (disorder), malignant neoplasm, no ICD-O subtype (morphologic abnormality), Expression Signature, papilla, Transcriptomes, localised Ewing's sarcoma/peripheral primitive neuroectodermal tumour, Condyles, onychodysplasia, peripheral primitive neuroectodermal tumor, face, Homo sapiens disease, Malignancies, Double-Stranded DNA, deoxyribonucleic acids, Pen19, DNAn, P19, Bony Apophyses, connective and soft tissue neoplasm, Tumors, Relapse, Ewsh, anatomical protrusion, Mesenchymal tumor, anon-Pen19, Expression Profiles, lamina, localised Ewing's tumour, flanges, Double-Stranded, localised Ewing's sarcoma, p19, Malignant neoplasm of other specified sites of connective and other soft tissue, Fs(3)Sz11, localized peripheral primitive neuroectodermal tumor, (Deoxyribonucleotide)n+m, Gene 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Bony Apophysis, DNA, other neoplasm, Bone, Ewing Sarcoma, Soft Tissue, peripheral primitive neuroectodermal tumour, other disease, Sarcoma of the Soft Tissue and Bone, DNS, (Deoxyribonucleotide)n, Transcriptome Profile, lamellae, Neoplasms, Spindle Cell Sarcomas, localised Ewing sarcoma, Benign Neoplasm, Gene, Malignant, process of organ, Deoxyribonucleic acids, and hypotrichosis, protrusion, lamella, site unspecified, Soft Tissue Sarcoma, Sarcoma of Soft Tissue, Deoxyribonucleic Acid, disease or disorder, [M]Sarcoma NOS (morphologic abnormality), Mood, DmF2, SARFH, Sarfh, Sarcoma of Soft Tissue and Bone, lod, Malignant neoplasm of connective and other soft tissue of upper limb, Sarcomas, Malignant Tumor of the Soft Tissue, Malignant neoplasm of connective and other soft tissue of head, Genetic, pattern, Malignancy, Tissues, distribution, Recrudescences, Profile, MAL NEO SOFT TIS THORAX, Malignant neoplasm of connective and other soft tissue of abdomen, Double Stranded, Deoxyribonucleic acid, ridges, tumor of soft tissue and skeleton, pen19, Recurrences., Ewing's Tumor, non-neoplastic, Neoplasias, Malignant tumor of soft tissue, Malignant Neoplasm of the Soft Tissue, disorder, Ewing's tumor, Apophysis, Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, (Deoxyribonucleotide)m, Spindle Cell Sarcoma, laminae, MAL NEO SOFT TISSUE ARM, MAL NEOPL TRUNK NOS, Cancer, Ewing's Family of Tumors, Connective Tissue Sarcoma, Malignant Soft Tissue Tumor, sarcoma, MAL NEO SOFT TISSUE LEG, Transcriptome, Apophyses, Malignant Neoplasm, malignant, DNAn+1, Affects, Malignant neoplasm of connective and other soft tissue of lower limb, disorders, medical condition, Ewing Family of Tumors, Cistrons, BcDNA:GM09207, Malignant neoplasm of connective and other soft tissue of thorax, AU018891, Bones and Bone, peripheral, [M]Sarcoma NOS, whole transcriptome, Ewing's sarcoma/peripheral primitive neuroectodermal tumor, PNET of Thoracopulmonary Region, Malignant neoplasm of connective and other soft tissue, MT, including shoulder, Epithelioid Sarcomas, MAL NEO SOFT TISSUE HEAD, Soft tissue tumour, Gene Expression Signatures, Tumors of the Ewing's Family, Neoplasm, core, TFIID, condition, Gene Expression Signature, bones, ds-DNA, Malignant mesenchymal tumour, WDR51A, flange, organ process, Caz, Ewing tumour, Epithelioid, Ewing sarcoma, Malignant neoplasm of connective and other soft tissue (disorder), osseous tissue, primary cancer, localised peripheral primitive neuroectodermal tumour, Ewings sarcoma-primitive neuroectodermal tumor, Ewings sarcoma, Soft Tissue Sarcomas, Ewing, cas, Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Cancers, Bones, Lds, Malignant Soft Tissue Neoplasm, malignant tumor, Ews, EWS, processes, Ewing's, mineralized bone tissue, no ICD-O subtype, Bone Tissue, Gene Expression Profiles, Fusions, Desoxyribonukleinsaeure, calcium tissue, Signature, bone organ, NeoplasiafalseWhole genome sequencing of Ewings SarcomaSarcomas are cancers of the bone and soft tissue often defined by their gene fusions. However, the timing, context, and processes by which these pathogenic fusions arise are unknown. We explored this in Ewing sarcoma, a cancer driven by EWSR1-ETS fusions, with very few cooperating mutations. Combining whole-genome sequencing with enhanced informatics, we found that the EWSR1-ETS fusion arose from striking rearrangement clusters in 42% of cases (52/124). Notably, these were organized in loops that universally contained the fusion at their center, while also weaving up to 18 genes together with it. We found the same pattern of rearrangements in three additional types of sarcoma. From these data, we define a new signature for sarcoma fusions that precedes other somatic changes, in the earliest replicating DNA of the genome. This dramatic, sudden process impinges on many genes – generating multiple coding changes that profoundly affect the transcriptome, with the disease-defining gene fusion at its core. These rearrangement loops emerge in an early ES clone from which both the primary tumor and the lethal relapse emerged, and then evolved in parallel until clinically detected.2019-03-13 15:52:59EGAS000010033859606EGAD00001004589EGAC00001001125