{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Nikoleta Juretic"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000048"],"host":["EGA"],"description":["EGA DAC EGAC00001000048"],"repository":["EGA"],"email":["nikoleta.juretic@affiliate.mcgill.ca"],"pubmed_abstract":["Pediatric midline high-grade astrocytomas (mHGAs) are incurable with few treatment targets identified. Most tumors harbor mutations encoding p.Lys27Met in histone H3 variants. In 40 treatment-naive mHGAs, 39 analyzed by whole-exome sequencing, we find additional somatic mutations specific to tumor location. Gain-of-function mutations in ACVR1 occur in tumors of the pons in conjunction with histone H3.1 p.Lys27Met substitution, whereas FGFR1 mutations or fusions occur in thalamic tumors associated with histone H3.3 p.Lys27Met substitution. Hyperactivation of the bone morphogenetic protein (BMP)-ACVR1 developmental pathway in mHGAs harboring ACVR1 mutations led to increased levels of phosphorylated SMAD1, SMAD5 and SMAD8 and upregulation of BMP downstream early-response genes in tumor cells. Global DNA methylation profiles were significantly associated with the p.Lys27Met alteration, regardless of the mutant histone H3 variant and irrespective of tumor location, supporting the role of this substitution in driving the epigenetic phenotype. This work considerably expands the number of potential treatment targets and further justifies pretreatment biopsy in pediatric mHGA as a means to orient therapeutic efforts in this disease."],"pubmed_title":["Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma."],"pubmed_authors":["Fontebasso Adam M AM, Papillon-Cavanagh Simon S, Schwartzentruber Jeremy J, Nikbakht Hamid H, Gerges Noha N, Fiset Pierre-Olivier PO, Bechet Denise D, Faury Damien D, De Jay Nicolas N, Ramkissoon Lori A LA, Corcoran Aoife A, Jones David T W DT, Sturm Dominik D, Johann Pascal P, Tomita Tadanori T, Goldman Stewart S, Nagib Mahmoud M, Bendel Anne A, Goumnerova Liliana L, Bowers Daniel C DC, Leonard Jeffrey R JR, Rubin Joshua B JB, Alden Tord T, Browd Samuel S, Geyer J Russell JR, Leary Sarah S, Jallo George G, Cohen Kenneth K, Gupta Nalin N, Prados Michael D MD, Carret Anne-Sophie AS, Ellezam Benjamin B, Crevier Louis L, Klekner Almos A, Bognar Laszlo L, Hauser Peter P, Garami Miklos M, Myseros John J, Dong Zhifeng Z, Siegel Peter M PM, Malkin Hayley H, Ligon Azra H AH, Albrecht Steffen S, Pfister Stefan M SM, Ligon Keith L KL, Majewski Jacek J, Jabado Nada N, Kieran Mark W MW"],"pubmed_title_synonyms":["tsri, fop, ActR-I, alk-2, actri, Acvrlk2, ACVR1A, xALK-2, SKR1, TSRI, acvrlk2, acvr1, ACVRLK2, ACTRI, midline, acvr1a, M disc, mesophragma, Mutations, Acvr, skr1, Alk-2, FOP, high-grade astrocytoma., Alk8, sax, ALK2, ActRIA, Tsk7L, alk8, D330013D15Rik, M line, alk2"],"name_synonyms":["the brain, synganglion, suprasegmental structures, suprasegmental levels of nervous system, encephalon, other neoplasm., Encephalon"],"pubmed_abstract_synonyms":["Pons, SMAD family member 1, Materials, smad-1, SMAD family member 5, lambdatop, HBGFR, SMAD family member 9, dev, acvr1, DNA Methylations, Tumor, TGFbeta-60A, Grade I Astrocytomas, TGFbeta, mesophragma, Mutations, x1fgfr, DmelCG9885, Subependymal Giant Cell Astrocytoma, CEK, responsivity, Cerebral Astrocytoma, madh5, Pilocytic Astrocytoma, madh4, Xmad1, Whole Transcriptome, Transcriptome Sequencing, Eask, JV4-1, Fs(3)Hor, Smad, placement, Bone Tissues, Dm-DPP, Fgf-r, FLG, treatment, cek, Biopsies, M(2)23AB, Gbb-60A, Tissue, Hspy, fgfr-1, NTef2, Astrocytoma, Epigenomic, flg, BTL/FGFR2, Fibrillary, p-Mad, Role Concepts, Protoplasmic Astrocytomas, Histone H5, Histone H4, Histone H7, Condyles, Homo sapiens disease, Tk2, Bony Apophyses, Ponte, Histone H1, Histone H3, Tumors, Pilocytic, Cerebral Astrocytomas, Exome, TGF-beta, bFGF-R-1, Anaplastic, Fs(3)Sz11, FOP, Benign, Role Concept, XFGFR-1, l(2)22Fa, DWFC, Role, relational spatial quality, smad10, Mixed Oligoastrocytomas, tsri, shv, Grade I Astrocytoma, Complete Transcriptome, fop, Gemistocytic Astrocytomas, 60A, Mad-related protein 1, mMad1, FGFR-1, TSRI, En(vvl), Grade III Astrocytomas, Benign Neoplasms, midline, M disc, Malignant Neoplasms, Phenotypes, Alk-2, pons cerebri, Material, JV41, Subependymal Giant Cell, Whole Exome Sequencing, CG2684, Dwf-A, Glioma, l(3)00208, Bony Apophysis, DNA, Epigenetics, other neoplasm, Protoplasmic, Dwf-C, ho, Grade II Astrocytoma, HRTFDS, MusMLP, Neoplasms, M(2)LS1, number, xsmad4, protein-containing complex, KAL2, Pleomorphic Xanthoastrocytomas, DmelCG5562, 2/23, xsmad9, SMAD 9, kal2, SMAD 5, Gene Products, MAD, disease or disorder, SMAD 1, Juvenile Pilocytic Astrocytoma, bfgfr, Histone H3.3, Pons Varolii, Pontes, Mat, Dpp, DPP, Complete, Exome Sequencings, fgfr1, Acvrlk2, Tissues, HMN5, FGFBR, GlyRS, mad, smad1, smad8, Sequencing, CG6714, E(zen)2, smad5, blk, Gemistocytic, Neoplasias, BMP, Whole Exome, l(2)k00237, Xanthoastrocytoma, Whole, FGFR, OGD, Tsk7L, Apophysis, Methylations, Cancer, Pilocytic Astrocytomas, FLT2, Malignant Neoplasm, Complete Exome Sequencings, Apophyses, TGF-b, smad8a, ogd, FLT-2, smad8b, Proteins, disorders, dpc4, Madh1, acvrlk2, CG5562, function, Madh5, dtk2, ACTRI, Histone, Cell, xfgfr1, N-SAM, Concept, Bones and Bone, Exome Sequencing, vgr/60A, fgf-r, native protein, mSmad5, Neoplasm, condition, flt2, gbb-60A, DSMAV, Dm-GBB, jv5-1, LBPA, osseous tissue, Grade I, increased number, xALK-2, Intracranial Astrocytomas, Childhood, Cancers, MFR, Bones, Lds, Histone H1(s), CG32134, xmad, CT20816, Gene Proteins, mineralized bone tissue, c28, Mixed Oligoastrocytoma, BSP1, calcium tissue, Dtk2, Fibrillary Astrocytoma, SixtyA, biopsy, bone organ, AI451355, Neoplasia, Bones and Bone Tissue, dFGFR, protein, DPP-C, apg, Astrocytomas, Varolii, acvr1a, CD331, osteogenic tissue, Histone H2b, Hin-d, Histone H2a, Grade II Astrocytomas, Bone and Bone, diseases, Roles, Transforming growth factor-beta-signaling protein 1, P-mad, DFGF-R1, Dwarfin-C, Concepts, diseases and disorders, cytopathology, Dwarfin-A, protein aggregate, l(2)60A-J, SMAD8B, Btl, SMAD8A, DFR2, Gemistocytic Astrocytoma, hSMAD1, MADH1, increased, MADH6, DmelCG2684, human disease, MADH5, DNA methylation maintenance, XSmad4alpha, Complete Exome Sequencing, Whole Transcriptome Sequencing, P-Mad, SKR1, DNA methylation, Dfr-2, tgfb-60A, Acvr, skr1, dMAD, dMad, Mothers against DPP homolog 9, Mothers against DPP homolog 5, Madh8, Madh9, hSmad5, Mothers against DPP homolog 1, Astroglioma, disease management, Therapies, Malignancies, MADH9, Flt-2, Therapy, Oligoastrocytoma, Astrocytic, Tg, CG9885, Varolius, Fgfr-1, Alk8, ALK2, Diseases, Genetic Materials, Gliomas, alk8, Genetic Material, M line, alk2, l(2)k17036, PMad, 1110051M15Rik, Gbb, GBB, Anaplastic Astrocytoma, histopathology, Epigenetic, alk-2, DmelCG32134, portion of bone tissue, Xsmad1, PPH2, Childhood Cerebral, Protoplasmic Astrocytoma, XFGFRA2, Condyle, ACVRLK2, Treatments, pSmad, CG12399, early, Tgfbeta-60A, Intracranial, disease, Bony, bone, Horka, c-fgr, Fs(3)Horka, Cistron, medical condition., pMAD, pMad, Fibrillary Astrocytomas, Transcriptome Sequencings, location, Bone, Methylation, accessory, other disease, Grade II, bis(monoacylglycerol) hydrogen phosphate, Complete Exome, jip, Benign Neoplasm, gcn, Gene, MADR1, Malignant, supernumerary, Pons Varolius, CMT2D, HH2, DmF2, Cerebral, lod, reactivity, flt-2, WES, Madr1, 0844/01, ActR-I, Genetic, Malignancy, BFGFR, Intracranial Astrocytoma, Childhood Cerebral Astrocytomas, MAD homolog 5, Anaplastic Astrocytomas, X1FGFR, MAD homolog 9, Juvenile Pilocytic, non-neoplastic, Grade III Astrocytoma, SMAD1, MAD homolog 1, SMAD8, Smad1, disorder, AW208770, Smad9, Smad5, AI528653, Astrocytic Gliomas, FGFR1, Smad8, Grade III, Childhood Cerebral Astrocytoma, protein complex, D-FGFR, Astrogliomas, Juvenile Pilocytic Astrocytomas, Cistrons, Pleomorphic, Juvenile, Tgfb-60, ActRIA, DmHD-311, Protein, Pleomorphic Xanthoastrocytoma, Mixed, bones, Complete Transcriptome Sequencing, BSP-1, actri, l(2)10638, ACVR1A, Mothers-against-DPP-related 1, Astrocytic Glioma, Protein Gene Products, present in greater numbers in organism, l(2)K00237, Mlp1, DmelCG12399, Therapeutic, Bone Tissue, sax, cardinality, HD-311, Treatment, H3(any), response, JV5-1, D330013D15Rik"],"additional_accession":[]},"is_claimable":false,"name":"McGill-DKFZ Pediatric Brain Tumour Consortium","description":"Data Access Committee EGAC00001000048","dates":{"output":"2025-1-9"},"accession":"EGAC00001000048","cross_references":{"TAXONOMY":["9606"],"pubmed":["24705250"],"EGA":["EGAS00001000720","EGAS00001001654","EGAS00001001014","EGAS00001000226","EGAS00001000721","EGAD00001000134","EGAD00001001055","EGAD00001000791","EGAD00001000792","EGAD00001002111"]}}