EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100110538EGA dataset EGAD00001001105EGARhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS.Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.Seki Masafumi M, Nishimura Riki R, Yoshida Kenichi K, Shimamura Teppei T, Shiraishi Yuichi Y, Sato Yusuke Y, Kato Motohiro M, Chiba Kenichi K, Tanaka Hiroko H, Hoshino Noriko N, Nagae Genta G, Shiozawa Yusuke Y, Okuno Yusuke Y, Hosoi Hajime H, Tanaka Yukichi Y, Okita Hajime H, Miyachi Mitsuru M, Souzaki Ryota R, Taguchi Tomoaki T, Koh Katsuyoshi K, Hanada Ryoji R, Kato Keisuke K, Nomura Yuko Y, Akiyama Masaharu M, Oka Akira A, Igarashi Takashi T, Miyano Satoru S, Aburatani Hiroyuki H, Hayashi Yasuhide Y, Ogawa Seishi S, Takita Junko J15 kDa phosphoprotein enriched in astrocytes, HCL3, Qa7, Q9, Qa9, Data Set, ped, HUMMAT1H, l(2)02029, GLUT-1, D15S12, DYT9, DYT18, DYT17, HMAT1, Dystonia 18, paroxysmal exertion-induced dyskinesia, paroxysmal exertion-induced dystonia with or without epilepsy and/or hemolytic Anaemia, paroxysmal exertion-induced dystonia with or without epilepsy and/or hemolytic Anemia, MAT1H, DmelCG6091, Qa-7., Enb, H-2Q7, ENA, Ena, EYCL, CG15112, DYT-SLC2A1, H-2Q9, ENA/VASP, Vasp, EYCL2, ped with or without epilepsy and/or hemolytic Anaemia, DmelCG15112, ENHANCER OF ATNSI ACTIVITY, SHEP1, EYCL3, GLUT1 deficiency syndrome 2, PEA-15, NDPP1, ped with or without epilepsy and/or hemolytic Anemia, P, paroxysmal exercise-induced dyskinesia with or without epilepsy and/or hemolytic Anaemia, MAT1, enb, VASP, GLUT1, HTLVR, Phosphoprotein enriched in diabetes, GLUT1DS, BEY2, BEY1, GLUT, EIG12, paroxysmal exercise-induced dyskinesia with or without epilepsy and/or hemolytic Anemia, Ped, PED, MENA, Qa-2, BOCA, BEY, GLUT1DS2, Qa-9WES, Complete Transcriptome, Complete, rostral migratory pathway, Complete Transcriptome Sequencing, Exome Sequencings, Transcriptome, Complete Exome Sequencings, Complete Exome, Transcriptome Profile, Complete Exome Sequencing, Profile, Whole Transcriptome Sequencing, Exome, Expression Profiles, RMS., Gene Expression Profile, Gene, Profiles, Signatures, Sequencing, Gene Expression, Exome Sequencing, Whole Exome, Expression Signature, Gene Expression Profiles, Whole, Expression Signatures, Gene Expression Signatures, Whole Exome Sequencing, Transcriptomes, Whole Transcriptome, Transcriptome Sequencing, Gene Expression Signature, Signature, RMS, Transcriptome Sequencings, Expression Profile, Transcriptome Profilesgenetic, determination, Epigenetic, malignant, chemical analysis, Rhabdomyosarcomas, familial, inherited genetic, assay, rhabdomyosarcoma., Epigenetics, constitutitional genetic, rhabdomyosarcoma (disease), hereditary, rhabdomyosarcoma, EpigenomicRAS, Ras, PRKBA, dp53, l(1)G0098, Akt/PKB, Materials, short stature, SOFT, DAKT1/PKB, DPTEN, Profiles, Ras-1, AKT1, soft, Mutations, ras, c-ras2, bbl, JTK2, TEP1, Cell Division Cycles, xPax3-B, xPax3-A, BCC7, beta-Tub6D, Tissue, dmp53, T, 1422/04, pax3, DNA Methylomes, Signatures, fgfr-4, Epigenomic, RacPK, high frequency, Expression Signature, Dp53, Bannayan-Riley-Ruvalcaba syndrome, onychodysplasia, CG17117, rhabdomyosarcoma (disease), connective and soft tissue neoplasm, p50/tubulin, CG1799, pseudopapilledema, CG10873, Ras2, RAS2, Ras1, RAS1, Methylomes, familial, AKT/PKB, PTEN3, Pax3, PTEN1, macrocephaly with multiple lipomas and hemangiomas, Expression Signatures, XFGFR-4, TKF, dRas85D, p-Akt, simple tissue, Bannayan-Zonana syndrome, bfy, ras1, Expression Profile, ras2, HTH, Hth, BcDNA:RE36103, Spindle Cell, Hras-1, CG3401, WS1, beta3Tub, beta3TUB, Dm Ras1, WS3, INSDC_feature:gene, RILEY-SMITH syndrome, PTENa, dAKT/dPKB, PKB/dAKT, DTB3, Phenotypes, RasI, Material, Epithelioid Sarcoma, bhy, DNA, Epigenetics, Pax-3, Harvey-ras, CG31325, Soft Tissue, Hras1, RAC-ALPHA, DNA Methylome, 2310035O07Rik, beta[[3]]-Tub, whole exome, DmelCG4006, DmelCG17117, GLM2, dRas, Rhabdomyosarcomas, Spindle Cell Sarcomas, number, CG1167, H-ras, Ruvalcaba -Myhre-Smith syndrome, DRAS1, DRas2, 143391_i_at, Prognostic Factors, beta3 TU, IMPDH, LFS1, rhabdomyosarcoma, LD06825, l(3)05745, Dras2, Dras1, morphology, Myhre-Riley-Smith syndrome, D-Ras, Soft Tissue Sarcoma, AI463227, Kras-2, CDHS, anon-EST:Liang-2.13, IMPdH, Ha-ras, Dras, Cycles, ras 1, Sarcomas, anatomy, fgfr4, raspberry/impd, Profile, Cell Division Cycle, cell-division cycle, tumor of soft tissue and skeleton, Ras[V12], EK3-4, DmelCG5671, DRas, DRas85D/Ras, Dmras64B, clustered, AKT, Akt, B430203M17Rik, beta[[3]]-tubulin, Spindle Cell Sarcoma, RMS, constitutitional genetic, Methylations, Dmbeta3, PTEN, akt, prac, RMS., beta3t, DAkt1, dPten, DAKT1, Factor, D-ras-1, pten, xfgfr4, Cell, Ruvalcaba-MYHRE-SMITH syndrome, E(faf), DmelCG1167, dpten, PKB, CWS6, Epithelioid Sarcomas, CWS1, p53/tubulin, Gene Expression Signatures, PKB-ALPHA, S35097, CG4006, dPTEN, Dakt1, CG33336, RAS85D, Mmac, Dmras85D, CG5671, l(1)9Eb, D-p53, Soft Tissue Sarcomas, Dm-P53, beta3, dtl, Tub, dAkt/PKB, Gene Expression Profiles, betatub60D, mesenchymal tumor, hereditary, RMSS, Ras1/RAs85D, Ruvalcaba-Myhre-Smith syndrome, and hemangiomata, Gene Expression Profile, histology, c-rasHa, E(sev)3C, betaTub3, CD334, Tp53, CG11485, DMP53, xpax3, Dmp53, tumour of soft tissue and skeleton, anatomy and histology, D-Ras1, macrocephaly pseudopapilledema and multiple hemangiomas, 1323/07, Prognoses, RTK, l(1)G0436, XFGFR-4a, ras85B, DmP53, ras85D, PKB|Akt, genetic, B3t, Sarcoma, DmelCG3401, D-ras-2, Cell Cycles, Transcriptomes, and multiple hemangiomata, Sp, fgfr-4c, single-organism behavior, l(3)s1747, dakt, Ki-ras, BRRS, Expression Profiles, l(3)89Bq, Fgfr-4, results, Division Cycles, 3t, Gene Expression, PKB/Akt, PKB/AKT, dAkt, dAKT, Genetic Materials, p21[Ras1], PIX2, dRas1, dRAS1, DAkt, Methylome, Dras85D, Tub60D, Genetic Material, ras-2, Transcriptome Profiles, l(3)04226, macrocephaly, DPKB, beta-tub, l(1)G0351, LD02673, Factors, histopathology, pAkt, Division Cycle, Epigenetic, DmelCG1799, c-Ha-ras, D-ras1, l(1)G0238, MMAC1, Prognostic, D-ras2, DmelCG33336, Exomes, C-ras1, common, pax-3, Dras64B, sarcoma of the soft tissue and bone, C-ras2, l(3)06677, l(1)G0002, l(1)G0482, hth1, Dakt, hth2, sarcoma of soft tissue and bone, Patient, c-H-ras, l(1)G0127, dPKB, facial dysmorphism, P53, p44, Cistron, inherited genetic, BZS, betaTub, Prognostic Factor, DRAC-PK85, RasV12, p50, Transcriptome Profile, Kras2, p53, Gene, DmelCG9375, presence, and hypotrichosis, l(1)G0388, Dpkb, MHAM, pax3a, pax3b, Cycle, l(1)G0380, p21B, rostral migratory pathway, dras1, Dm-ras-64B, clone 2.13, Genetic, D.m.BETA-60D, clumped, Cell Division, l(1)G0391, Ras 85D, Trp53, Clients, betaTub60C, DRAC-PK, beta3-tubulin, TRP53, Riley-Smith syndrome, ras-l, macrocephaly multiple lipomas and hemangiomata, l(1)G0056, beta-Tub60D, sarcoma, Transcriptome, Dm-HTH, splotch, CG9375, malignant, HUP2, BETA 60D, beta3-Tub, K-ras, multiple lipomas, Cistrons, Client, Xp53, count in organism, fs(3)05703, EP(X)1093, D-Akt, Gene Expression Signature, methylation, AI929937, beta[[3]] tubulin, WDR51A, Epithelioid, frequent, distinct, 10q23del, Epigenomes, akt1, dAkt1, DRAC-PK66, beta60C, l(3)86Ca, A130070J02Rik, Su(tor)3-2, DEC, Meis1, dakt1, Bannayan syndrome, PKBalpha, cardinality, dAKT1, RAC, Rac, Signaturefalseena-DATASET-UT-Ped-15-12-2014-06:44:14:477-357 - samplesWhole-exome sequencing in 16 RMS cases Whole-transcriptome sequencing in 8 RMS cases2017-07-26 15:39:25EGAD00001001105960626138366EGAC00001000207EGAS00001000884