EGAGenomicsIllumina Genome Analyzer IIx, Illumina HiSeq 2000Whole Genome Sequencinghttps://ega-archive.org/studies/EGAS00001000505EGAEGA study EGAS00001000505Whole genome sequence of condrosarcomaIndel/point mutation of chondrosarcomarestrictedEGAChondrosarcoma is the second most frequent malignant bone tumor. However, the etiological background of chondrosarcomagenesis remains largely unknown, along with details on molecular alterations and potential therapeutic targets. Massively parallel paired-end sequencing of whole genomes of 10 primary chondrosarcomas revealed that the process of accumulation of somatic mutations is homogeneous irrespective of the pathological subtype or the presence of IDH1 mutations, is unique among a range of cancer types, and shares significant commonalities with that of prostate cancer. Clusters of structural alterations localized within a single chromosome were observed in four cases. Combined with targeted resequencing of additional cartilaginous tumor cohorts, we identified somatic alterations of the COL2A1 gene, which encodes an essential extracellular matrix protein in chondroskeletal development, in 19.3% of chondrosarcoma and 31.7% of enchondroma cases. Epigenetic regulators (IDH1 and YEATS2) and an activin/BMP signal component (ACVR2A) were recurrently altered. Furthermore, a novel FN1-ACVR2A fusion transcript was observed in both chondrosarcoma and osteochondromatosis cases. With the characteristic accumulative process of somatic changes as a background, molecular defects in chondrogenesis and aberrant epigenetic control are primarily causative of both benign and malignant cartilaginous tumors.Unique mutation portraits and frequent COL2A1 gene alteration in chondrosarcoma.Totoki Yasushi Y, Yoshida Akihiko A, Hosoda Fumie F, Nakamura Hiromi H, Hama Natsuko N, Ogura Koichi K, Yoshida Aki A, Fujiwara Tomohiro T, Arai Yasuhito Y, Toguchida Junya J, Tsuda Hitoshi H, Miyano Satoru S, Kawai Akira A, Shibata Tatsuhiro TComplete Genome Sequencing, Genome Sequencing, Complete, Complete Genome, Whole Genome, Cartilaginous cancer, Chondrosarcomas, primary chondrosarcoma of the bone, CHDSA., chondrosarcoma of bone, Whole, SequencingMutations, Pan-genome, Materials, Genetic, Cartilaginous cancer, Genomes, Material, chondrosarcoma of bone, Core Genome, Accessory Genome, Genetic Materials, Cistron, Gene, Mutations., Chondrosarcomas, primary chondrosarcoma of the bone, Cistrons, CHDSA, Pangenome, Genetic MaterialCOL11A3, Col2a-1, Del1, Lpk, Materials, frequent, Genetic, Cartilaginous cancer, collagen II, M100856, Rgsc856, Gene, INSDC_feature:gene, Cistrons, COLLII, AOM, STL1, Mutations, high frequency, Dmm, Portraits, cartilage collagen, Material, CHDSA., Col2a, chondrosarcoma of bone, ANFH, Col2, Genetic Materials, COL2A1, Cistron, SEDC, CG2A1A, Chondrosarcomas, primary chondrosarcoma of the bone, Genetic Materialcancer of skeletal element, EXT, Col2a-1, bone tumor, Materials, single-organism developmental process, transforming growth factor beta ligand binding to type I receptor, malignant tumor of the bone, postnatal development, acvr2, growth and development, protein, osseous tumour, Tumor, DPP-C, chondromatous neoplasm, TGFbeta-60A, malignant osseous tumor, prevention, TGFbeta, Mutations, Hin-d, DmelCG9885, ACVR2, Col2a, cartilage biosynthesis, type I, AI314845, TactrII, TGFbeta receptor binding, Extracellular Matrices, protein aggregate, l(2)60A-J, prevention and control, Id-1, Dyschondroplasia, PICD, Dm-DPP, multiple osteochondromas, malignant skeletal element neoplasm, reference sample, Genomes, M(2)23AB, Idpc, neoplasm of the cartilage, M100856, Gbb-60A, malignant tumor of bone, chromatid, tgfb-60A, Epigenomic, BC042768, preventive measures, Prostatic Neoplasm, activin, high frequency, TGF-beta receptor binding, Cancer of the Prostate, malignant neoplasm, chondrosarcoma of bone, IDPC, Ollier disease, osseous tumor, inhibin, actrii, s, Ollier type, Malignancies, SEDC, tumor of the cartilage, multiple cartilaginous enchondroses, Tumors, malignant bone tumor, cancer of the prostate, preventive therapy, anatomical protrusion, aberrant, IDH, familial, TGF-beta, Tg, FNZ, IDP, cartilage formation, enchondromatosis, dyschondroplasia, CG9885, multiple caused by mutation in EXT1, Kast's syndrome, bone tumour, INSDC_feature:misc_RNA, IDCD, CIG, Benign, osteochondromatosis, Ollier's disease, l(2)22Fa, Fn-1, cancer of the bone, Genetic Materials, NOS, COL2A1, ED-B, Acvr2, bone cancer, primary chondrosarcoma of the bone, END, Genetic Material, l(2)k17036, shv, Idh-1, FSH-Releasing, COL11A3, Gbb, GBB, 60A, FN, Epigenetic, cartilaginous neoplasm, malignant osseous tumour, transforming growth factor beta receptor anchoring activity, malignant neoplasm of the bone, Benign Neoplasms, INSDC_feature:gene, skeletal element cancer, FSH-Releasing Protein, cancer of prostate, CHDSA, Malignant Neoplasms, Tgfbeta-60A, Dmm, Fn, multiple, Chromosome, spine, Material, chondrogenic neoplasm, Col2, Cistron, malignant tumour of bone, GFND, Epigenetics, EXT1 exostoses, Prostate, ActrIIa, Malignant Neoplasms., atypia, localised, ho, rActR-II, Prostate Neoplasms, bis(monoacylglycerol) hydrogen phosphate, Neoplasms, M(2)LS1, number, Benign Neoplasm, Matrix, gcn, Gene, chondromatous tumor, malignant bone tumour, CA - bone cancer, Matrices, protein-containing complex, bone neoplasm, Malignant, presence, protrusion, DmelCG5562, Core Genome, malignant neoplasm of bone, Prostatic Cancers, Gene Products, malignant osseous neoplasm, atypical, RGD1566176, Cancer of Prostate, HEL-216, AI788952, Prostate Cancers, matrisome, Dpp, DPP, Lpk, localized, Genetic, Cartilaginous cancer, Malignancy, enchondromatosis with haemangiomata, Osteochondromatoses, Accessory Genome, Rgsc856, cancer of bone, cartilage organ development, E030024J03Rik, blk, Neoplasias, MSF, BMP, malignant bone neoplasm, cartilage collagen, Extracellular, diaphyseal Aclasis, Prostatic, CG2A1A, HHT1, Activin, Controlled, Cancer, hereditary prostate cancer, ACTRII, Controlling, malignant tumour of the bone, Del1, Malignant Neoplasm, Edg, TGF-b, protein complex, chondrogenic tumor, Proteins, cartilage biogenesis, CG5562, defective, FINC, Cistrons, LETS, Pangenome, E330027I09, malignant neoplasm of skeletal element, STL1, Tgfb-60, development, count in organism, prophase chromosome, FSH Releasing Protein, vgr/60A, MT, cartilaginous tumor, native protein, Prostatic Cancer, Protein, HEL-S-26, Neoplasm, ANFH, transforming growth factor beta receptor ligand, background, gbb-60A, exostoses, multiple enchondromatosis, chondrogenesis, Dm-GBB, LBPA, primary cancer, transforming growth factor beta, frequent, neoplasm of cartilage, tumor of cartilage, l(2)10638, interphase chromosome, collagen II, prophylaxis, postnatal growth, multiple cartilaginous exostoses, Cancers, malignant tumor, transforming growth factor beta ligand binding to type II receptor, COLLII, introduction, Prostate Neoplasm, AOM, Protein Gene Products, Gene Proteins, Pan-genome, control, cartilage element development, mKIAA1197, prostate cancer, PC, GFND2, ORW1, SixtyA, Chondrosarcomas, Prostate Cancer, growth, osseous cancer, NeoplasiafalseWhole genome sequencing of chondrosarcomaMassive parallel sequencing of 10 chondrosarcoma genomes was conducted to identify somatic mutations, structural alterations including fusion genes and mutation signatures that may help to comprehensively characterize the molecular features.2017-07-26 15:39:25EGAS00001000505960625024164EGAD00001000873EGAD00001000874EGAC00001000010