{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000506"],"host":["EGA"],"description":["EGA study EGAS00001000506"],"dataset_title":["EGAS00001000506_expression_2","Array_dataset_ega_box_64","Array_dataset_1","ATRT RNASeq","EGAS00001000506_expression_1","Title not provided","ATRT ATACSeq","ATRT ChIPSeq H3K27ac","ATRT whole exome sequencing"],"repository":["EGA"],"category":["restricted"],"description_synonyms":["xnotch, neoplasia, mSNF5, Tumor, Long Term, decapentaplegic receptor signaling pathway, NOTCH, BSAC, BCR, symptoms, CG40494, synganglion, SNF5 homolog, notch, Effect, placement, BCR1, Gene Expressions, Genomes, Bsac, cell process disease, tumor disease, neoplasm (disease), rhabdoid tumour predisposition syndrome, Ax, suprasegmental levels of nervous system, rhabdoid tumor predisposition syndrome, Epigenomic, genetic, decapentaplegic receptor signalling pathway, AI853148, RDT, set, high frequency, notch1-a, SNF5, co, Snf5, Xotch, tumor, SWNTS1, TL, SNF5|INI1, Long-Term Effects, NECD, EG:140G11.1, l(1)N, Tumors, swb, screening, suprasegmental structures, wide/broad, dpp signaling pathway, aberrant, Chp, Co, FLMKL1, familial, Longterm Effect, AMKL, neoplastic disease, tumours, D22S662, BRG1-associated factor 47, shd, relational spatial quality, fa, activation, decapentaplegic signaling pathway, AI561783, xnotch1, MRTF-A, Epigenetic, Encephalon, INI1, Ini1, Exomes, signs, Tcad, whole genome, CG17960, AU020204, Phenotypes, wide, clone 1.12, Mrtf-a, Integrase interactor 1 protein, inherited genetic, notch-1, TAN1, Epigenetics, other neoplasm, location, n[fah], MKL1met, LRPDIT, Gruppe, the brain, Dmel_CG00000, atypia, whole exome, localised, Mrtf-A, Effects, Neoplasms, bone morphogenetic protein signaling pathway, 5133400C09Rik, number, EG:163A10.2, Gene, broad, presence, NEOPL, SNF5L1, CML, CG17617, dpp receptor signalling pathway, hSNFS, rhoGAP1A, atypical, l(1)3Cb, MAL, Mal, neoplasm, BMP receptor signaling pathway, CDHH, l(1)Ax, DmelCG40494, Longterm, D22S11, DmelCG3936, hSNF5, Cdht, PHL, tumour, dNotch, EG:23E12.5, Long-Term, Expressions, EG:23E12.2, dpp receptor signaling pathway, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), BMP signalling pathway, Baf47, 4932416G01Rik, BAF47, grupos, LRP-DIT, Long-Term Effect, Expression, bone morphogenetic protein signalling pathway, NICD, constitutitional genetic, SNF5/INI1, Methylations, Neoplastic Growth, CT13012, ALL, 16-178, P105, 16-55, findings, grupo, defective, anon-EST:Liang-1.12, encephalon, Snr1, group, count in organism, neoplastic growth, MELODY, RTPS1, CG40453, spl, Long Term Effects, T-cadherin, focal, 1.1, Sfh1p, methylation, nd, MRD15, distinct., Exhibit, frequent, distinct, ensemble, Rest, disease of cellular proliferation, Longterm Effects, PPP1R144, cardinality, mKIAA3017, CG3936, hereditary, groupe, NEOPLASMS BENIGN, Neoplasia"],"name_synonyms":["rhabdoid tumour predisposition syndrome, atypia, assay, atypical, rhabdoid tumor predisposition syndrome., defective, other neoplasm, determination, aberrant, chemical analysis"],"additional_accession":[]},"is_claimable":false,"name":"Comprehensive analysis of atypical teratoid rhabdoid tumour (ATRT) using genomic, epigenomic and transcriptomic techniques.","description":"ATRTs (Atypical teratoid rhabdoid tumours) represent one of the most aggressive pediatric brain cancers, but intriguingly exhibit few other recurrently mutated loci except for  SMARCB1/hSNF5.  We integrated whole genome (n=15), exome, copy number, gene expression and methylation analyses to comprehensively interrogate 64 ATRTs and observed that structural events were relatively frequent in the ATRT genome (~3 tumour).  In addition to SMARCB1, which was targeted by structural events in a majority (49/64) of tumours, recurrent structural alterations targeting the LRP1B, CDH13, BCR and MKL1 loci were observed. We observed novel translocation events, including 2 targeting SMARCB1 which were detected only by NGS analyses. Significantly, integration of gene expression and methylation profiles with genomic analyses revealed ATRT comprise two sub-groups with distinct clinical and genetic features.  Group 1 tumours were characterized by supra-tentorial brain location, focal intragenic alterations of SMARCB1 and a pro-neural gene expression signature with evidence of NOTCH pathway activation.  While Group 2 ATRTs were characterized by infra-tentorial brain location, broad SMARCB1 alterations and an activation of the BMP signalling pathway. Our findings highlight epigenetic mechanisms as important determinants of ATRT tumour phenotypes, and demonstrate for the first time that ATRTs arising in different anatomical compartments comprise distinct molecular and therapeutic sub-groups.","dates":{"updated":"2019-10-31 12:52:11"},"accession":"EGAS00001000506","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00010000789","EGAD00010001546","EGAD00001004837","EGAD00001004847","EGAD00010000790","EGAD00010000710","EGAD00001004836","EGAD00010000712","EGAD00010001433","EGAD00001004576","EGAC00001000306"]}}