{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000572"],"host":["EGA"],"description":["EGA study EGAS00001000572"],"dataset_title":["DIPG_ICR_WGS","DIPG_ICR_WES"],"category":["restricted"],"repository":["EGA"],"pubmed_abstract":["Diffuse intrinsic pontine gliomas (DIPGs) are highly infiltrative malignant glial neoplasms of the ventral pons that, due to their location within the brain, are unsuitable for surgical resection and consequently have a universally dismal clinical outcome. The median survival time is 9-12 months, with neither chemotherapeutic nor targeted agents showing substantial survival benefit in clinical trials in children with these tumors. We report the identification of recurrent activating mutations in the ACVR1 gene, which encodes a type I activin receptor serine/threonine kinase, in 21% of DIPG samples. Strikingly, these somatic mutations (encoding p.Arg206His, p.Arg258Gly, p.Gly328Glu, p.Gly328Val, p.Gly328Trp and p.Gly356Asp substitutions) have not been reported previously in cancer but are identical to mutations found in the germ line of individuals with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP) and have been shown to constitutively activate the BMP-TGF-β signaling pathway. These mutations represent new targets for therapeutic intervention in this otherwise incurable disease."],"pubmed_title":["Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma."],"pubmed_authors":["Taylor Kathryn R KR, Mackay Alan A, Truffaux Nathalène N, Butterfield Yaron Y, Morozova Olena O, Philippe Cathy C, Castel David D, Grasso Catherine S CS, Vinci Maria M, Carvalho Diana D, Carcaboso Angel M AM, de Torres Carmen C, Cruz Ofelia O, Mora Jaume J, Entz-Werle Natacha N, Ingram Wendy J WJ, Monje Michelle M, Hargrave Darren D, Bullock Alex N AN, Puget Stéphanie S, Yip Stephen S, Jones Chris C, Grill Jacques J"],"name_synonyms":["Complete Genome Sequencing, average, Intrinsic., Genome Sequencing, Complete, Complete Genome, Whole Genome, other neoplasm, diffuse, Whole, Sequencing, scattered"],"description_synonyms":["Pons, Materials, PhrB photolyase activity, Period Prevalence, neoplasia, Tumor, pigmented epithelium, Varolii, Post-Mortem., H3/c, Mutations, Histone H2b, Histone H2a, Readability, Techniques, Point Prevalence, H3-f, Method, L-glutamic acid dipinacoline ester, Point Prevalences, 3, synganglion, Whole Transcriptome, Transcriptome Sequencing, NUP96, cytopathology, epithelium, placement, average, treatment, Prognoses, Gene Expressions, Biopsies, Post-Mortem Examinations, DIPG Brain Tumors, Prevalences, cell process disease, tumor disease, Complete Exome Sequencing, neoplasm (disease), Whole Transcriptome Sequencing, pigmented retina, Brain Tumor, suprasegmental levels of nervous system, DNA cyclobutane dipyrimidine photolyase activity, SURGICAL AND MEDICAL PROCEDURES, H3.3A, SUPPRESSOR OF AUXIN RESISTANCE 3, H3/d, Methodological Studies, H3/l, disease management, Histone H5, Therapies, Histone H4, Histone H7, Malignancies, tumor, Postmortem Examinations, Post-Mortem Examination, Ponte, Histone H1, Histone H3, Tumors, close to, Therapy, PRE, Prevalence, suprasegmental structures, frequency, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Exome, Genome Sequencing, neoplastic disease, Procedure, Varolius, Post-Mortem, tumours, Benign, Complete Genome, Postmortem, retinal pigment, dipyrimidine photolyase (photosensitive), Genetic Materials, median, relational spatial quality, retinal pigment layer, Genetic Material, infiltrative brainstem glioma, Complete Transcriptome, Factors, H3FD, histopathology, death rate, H3FC, polycomb repressive complex 2, Prognostic, H3-53, Encephalon, H3FL, Benign Neoplasms, Methodological, Diffuse Intrinsic Pontine Glioma, Children, surveillance, Methodological Study, morbidity, Treatments, Malignant Neoplasms, Autopsies, pons cerebri, metastatic, phr A photolyase activity, DNA-photoreactivating enzyme, hyaline, Patient, Material, Whole Exome Sequencing, Cistron, other neoplasm, H3F3, location, Transcriptome Sequencings, Prognostic Factor, the brain, Procedures, Extra Sex Combs/Enhancer of Zeste complex, Complete Exome, Neoplasms, Benign Neoplasm, Gene, Prognostic Factors, Period Prevalences, photoreactivating enzyme activity, Malignant, h3f3a, DIPG, Pons Varolius, NEOPL, Intervention or Procedure, Studies, stratum pigmentosa retinae, neoplasm, Technique, Histone H3.3, Pons Varolii, Pontes, h3.3a, h3.3b, WES, Postmortem Examination, Complete, MOS3, Whole Genome, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Exome Sequencings, Genetic, PRC2 complex, Malignancy, PRECOCIOUS, occurrence, interventionDescription, prevalence, Complete Genome Sequencing, F23A5.3, Interventional, tumour, Expressions, DIPG Brain Tumor, Sequencing, Examination, Neoplasias, Study, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS), Whole Exome, time of survival, Clients, Whole, Expression, DiPG, Neoplastic Growth, F23A5_3, incidence, Cancer, Intervention Strategies, Malignant Neoplasm, Complete Exome Sequencings, Factor, Cistrons, encephalon, Histone, Client, near to, Exome Sequencing, neoplastic growth, MODIFIER OF SNC1, survival, Period, Examinations, deoxyribonucleic photolyase activity, Neoplasm, H3|d, H3|c, H3|l, outbreaks, Intervention, RPE, Complete Transcriptome Sequencing, distinct, photolyase activity, H3.1, Cancers, Understanding, disease of cellular proliferation, Histone H1(s), endemics, p. pigmentosa retinae, h3.3, diffuse midline glioma, clear, Therapeutic, approaches, Point, vicinity of, epidemics, Treatment, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Post Mortem Examination, biopsy, NEOPLASMS BENIGN, Neoplasia"],"pubmed_title_synonyms":["tsri, infiltrative brainstem glioma, fop, ActR-I, DIPG Brain Tumors, alk-2, actri, Acvrlk2, ACVR1A, xALK-2, SKR1, TSRI, DIPG Brain Tumor., acvrlk2, acvr1, Brain Tumor, Diffuse Intrinsic Pontine Glioma, ACVRLK2, ACTRI, DIPG, acvr1a, Acvr, Mutations, skr1, Alk-2, diffuse midline glioma, FOP, Alk8, sax, ALK2, ActRIA, Tsk7L, alk8, D330013D15Rik, alk2"],"pubmed_abstract_synonyms":["Pons, MGC130048, Materials, glial tumors, Serine-Threonine Protein Kinases, Receptors, A4, Mixed Glioma, acvr1, Progress Reports, Tumor, DPP-C, TGFbeta-60A, Varolii, \"Myositis ossificans progressiva\" EXACT [SNOMEDCT_2005_07_31:205527009], acvr1a, TGFbeta, 2-Amino-3-hydroxypropionic acid, Mutations, Hin-d, Serine-Threonine Kinase, DmelCG9885, [M]Glioma NOS (morphologic abnormality), diseases, FL-SRAG, Summary Report, L-glutamic acid dipinacoline ester, [M]Gliomas (morphologic abnormality), diseases and disorders, synganglion, Protein Kinases, Kinase, Receptor-like Kinase, l(2)60A-J, Summary Reports, Dm-DPP, signal transduction by protein phosphorylation, gamma sarcoglycan, human disease, glioma (morphologic abnormality), Progress Report, DIPG Brain Tumors, M(2)23AB, Gbb-60A, SKR1, Neoplasm of the Neuroglia, C81330, Brain Tumor, suprasegmental levels of nervous system, Serine Threonine Protein Kinase, tgfb-60A, SURGICAL AND MEDICAL PROCEDURES, Germ-Line, Acvr, Progress, skr1, Field Reports, 2-amino-3-hydroxypropanoic acid, malignant neoplasm, Protein-Serine-Threonine, Therapies, Gliomas (morphologic abnormality), gamma-sarcoglycan, Protein Serine Kinase, Homo sapiens disease, Malignancies, Protein-Serine-Threonine Kinase, Ponte, \"progressive ossifying myositis\" EXACT [CSP2005:1982-9828], Tumors, Therapy, Glioma (except Nasal glioma, suprasegmental structures, Protein-Serine-Threonine Kinases, inborn, SG-gamma, TGF-beta, signal transduction by conformational transition, Tg, obsolete_glioma, Germ-Line Cell, Malignant Glioma, CG9885, Receptor-Like Kinases, Procedure, Varolius, signal transduction by trans-phosphorylation, signaling cascade, FOP, Fop, Benign, Alk8, Investigative Report, 3-Hydroxyalanine, ALK2, l(2)22Fa, Diseases, Gamete, Genetic Materials, Germ Cell, sarcoglycan, median, Gliomas, alk8, \"progressive myositis ossificans\" EXACT [ICD9CM_2006:728.11], Glial Cell Tumor, Serine Threonine Kinases, Serine-Threonine, Genetic Material, alk2, l(2)k17036, tsri, shv, Srag, Protein Serine Threonine Kinases, infiltrative brainstem glioma, fop, Gbb, GBB, 60A, 4930553O10Rik, death rate, alk-2, Field, TSRI, Benign Neoplasms, Tumor of Neuroglia, INSDC_feature:gene, Protein-Threonine, Diffuse Intrinsic Pontine Glioma, ACVRLK2, gamma (35kDa dystrophin-associated glycoprotein), Children, Serine Threonine Kinase, Treatments, Malignant Neoplasms, Tgfbeta-60A, Alk-2, disease, SRAG, pons cerebri, Report, DMDA, Protein Threonine Kinase, signaling pathway, Material, Tumor of the Neuroglia, 35kD dystrophin-associated glycoprotein, Cells, RP1-178F15.2, srag, not neoplastic), Cistron, L Serine, medical condition., Glioma, malignant (morphologic abnormality), L-Serine, Protein Kinase, Neoplasms of Neuroglia, Myositis Ossificans Progressiva, the brain, Glioma NOS, other disease, 2500003M10Rik, ho, SGCG_HUMAN, bis(monoacylglycerol) hydrogen phosphate, Activin Receptor-like Kinase, Neoplasms, M(2)LS1, Activin Receptor-Like Kinases, Benign Neoplasm, Protein Serine-Threonine, connatal, gcn, Gene, Neuroglial Tumor, Malignant, DIPG, Pons Varolius, TYPE, Germ Lines, Fibrodysplasia Ossificans Progressiva, Intervention or Procedure, DAGA4, Protein-Serine Kinase, DmelCG5562, Germ Line, Investigative, 35DAG, disease or disorder, Germ Line Cells, Progressive Ossifying Myositis, MAM, gamma-SG, Mixed Gliomas, SCG3, Pons Varolii, Pontes, Gametes, myositis ossificans progressiva, C1orf77, Dpp, DPP, Serine-Threonine Kinases, ActR-I, Genetic, Glioma NOS (morphologic abnormality), Malignancy, interventionDescription, Acvrlk2, Activin Receptor like Kinase, Interventional, Glial Neoplasm, DIPG Brain Tumor, \"Myositis ossificans progressiva\" EXACT [SNOMEDCT_2005_07_31:240121004], non-neoplastic, blk, Neoplasias, c1orf77, BMP, signalling pathway, Serine Threonine Protein Kinases, Progressive Myositis Ossificans, \"progressive myositis ossificans (disorder)\" EXACT [SNOMEDCT_2005_07_31:82725007], SRAG-5, Activin Receptor Like Kinases, time of survival, Protein Serine Threonine Kinase, SRAG-3, disorder, signal transduction by cis-phosphorylation, Tsk7L, [M]Gliomas, Investigative Reports, Tumors of Neuroglia, Activin, DiPG, Cancer, Intervention Strategies, pp7704, Malignant Neoplasm, TGF-b, 35 kDa dystrophin-associated glycoprotein, malignant, disorders, Protein-Threonine Kinase, acvrlk2, CG5562, medical condition, Germ, ACTRI, Cistrons, encephalon, Cell, SGCG, LGMD2C, Tgfb-60, Serin, vgr/60A, survival, MT, ActRIA, Research Reports, Neoplasm, Protein-Serine, condition, Mixed, Threonine Kinase, [M]Glioma NOS, gbb-60A, signalling cascade, Dm-GBB, Intervention, Glial Tumor, Germ-Line Cells, NOS (except Nasal glioma, Serine-Threonine Protein Kinase, LBPA, primary cancer, Serine Kinase, Neuroglial Neoplasm, DMDA1, Neuroglial Neoplasms, actri, Kinases, l(2)10638, ACVR1A, Glial Cell, xALK-2, Malignant glioma, Cancers, malignant tumor, Activin Receptor-like, Neoplasm of Neuroglia, diffuse midline glioma, no ICD-O subtype, Reports, Therapeutic, sax, Activin Receptor, SCARMD2, Glial Cell Tumors, Activin Receptor-Like, Malignant Gliomas, Treatment, Receptor, SixtyA, Summary, D330013D15Rik, \"Myositis Ossificans Progressiva\" EXACT [NCI2004_11_17:C3040], Neoplasia, Field Report"],"additional_accession":[]},"is_claimable":false,"name":"Whole genome sequencing of tumour and normal paired samples of diffuse intrinsic pontine gliomas","description":"Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing on a series of 20 tumour normal pairs of pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing on a further six tumour normal pairs obtained at autopsy.","dates":{"updated":"2019-10-31 12:52:10"},"accession":"EGAS00001000572","cross_references":{"TAXONOMY":["9606"],"pubmed":["24705252"],"EGA":["EGAD00001000706","EGAD00001000705","EGAC00001000148"]}}