EGAGenomicsILLUMINA, Illumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001002328EGAEGA study EGAS00001002328HERBY trial RNASeqHERBY trial WESrestrictedEGAgrade 3/4, high grade, Intervention Study.glial cell tumor, DmErk, extracellular signal-regulated kinase activity, pp44mapk, RNA Sequence Determination, GLM, Laboratory, PNT-P1, Sequence Determination, RNA Sequence, A4, Mixed Glioma, EY3-1, ALPHA-thalassemia/mental retardation syndrome, Tumor, Diagnosis, Xnp, XNP, hTRT, Grade I Astrocytomas, Prp4 protein kinase activity, mesophragma, Mutations, DmelCG8318, Multinucleated Giant, malignant Neuroglial tumor, hierarchy, Subependymal Giant Cell Astrocytoma, LeMPK3, ATP-protein transphosphorylase activity, Biological, systematics, type I, p44mpk, lamina pallidi incompleta, tumor of the neuroglia, Cerebral Astrocytoma, ATP:protein phosphotransferase (non-specific) activity, symptoms, Pilocytic Astrocytoma, Dp38, [M]Gliomas (morphologic abnormality), Whole Transcriptome, Transcriptome Sequencing, AA120551, malignant" EXACT [SNOMEDCT_2005_07_31:189909006], Analysis, D-ets-2, 3520, Research Activity, SAPK2, Laboratory Research, SEM, Sem, well differentiated, Id-1, peripheral type, PICD, Priorities, Multicase, MAP-k, gamma sarcoglycan, glioma (morphologic abnormality), E030030H24Rik, Analyses, pp42, proportionality to, Idpc, Neoplasm of the Neuroglia, Dsor2, sem, Sequence Determinations, high grade, Astrocytoma, Fibrillary, IDPC, sample, tumour of neuroglia, Histone H5, Protoplasmic Astrocytomas, Gliomas (morphologic abnormality), Histone H4, Histone H7, Mvasi, Histone H1, Hp1bp38, Diagnose, Histone H3, Tumors, ERK-A, p82 kinase activity, screening, dpERK, dpErk, lamina medullaris accessoria, Pilocytic, Cerebral Astrocytomas, Exome, betaIIPKC, Systematics, Research Priorities, DmMAPK, Malignant Glioma, Alpha thalassemia mental retardation syndrome, Alpha thalassemia intellectual disability syndrome, PMK-2, Giant Cell, dp-ERK, PMK-1, Anaplastic, Diagnoses, SHS, PMK-3, Wee-kinase activity, Postmortem, Recklinghausen's disease, MRXS3, pMAPK, pMapK, sarcoglycan, END, Mixed Oligoastrocytomas, Research and Development, Grade I Astrocytoma, grade 3/4, Idh-1, Complete Transcriptome, pntP2, DmERKA, Gemistocytic Astrocytomas, Pointed-P1, rl/MAPK, death rate, TCS1, G1, Ets94F, proportionality, signs, non-specific serine/threonine protein kinase activity, Cerebri, ZNF-HX, Grade III Astrocytomas, rate, Tumor of Neuroglia, l(2)41Ac, midline, Children, Age, M disc, Activities, Phenotypes, ALPHA-thalassemia/intellectual disability syndrome, CT34260, dpERk, label, 35kD dystrophin-associated glycoprotein, serine-specific protein kinase activity, Cells, Whole Exome Sequencing, Subependymal Giant Cell, SAPK, HIPK2, cytidine 3', not neoplastic), Glioma, glial neoplasm, WSS, malignant (morphologic abnormality), Wee 1-like kinase activity, Protoplasmic, Neoplasms of Neuroglia, AA473386, AA407358, Glioma NOS, 0998/12, X-linked, glycogen synthase A kinase activity, Grade II Astrocytoma, glycogen synthase kinase 3 activity, neuroglial tumor, number, 12559, Neuroglial Tumor, h3f3a, phosphorylase b kinase kinase activity, EK2-1, Pleomorphic Xanthoastrocytomas, morphology, DMPOINT1A, Screening, Antemortem, TP2, MAM, gamma-SG, ribosomal protein S6 kinase II activity, Sanger sequencing, Juvenile Pilocytic Astrocytoma, Histone H3.3, Erk, ERK, PRKM1, PRKM2, protein-serine kinase activity, proportion, anatomy, Complete, Exome Sequencings, pointed-RC, Glioma NOS (morphologic abnormality), Academic, Multinucleated Giant Cells, scattered, lamella pallidi incompleta, STK32, C87398, accessory medullary lamina of pallidum, Glial Neoplasm, Diagnoses and Examinations, Nf-1, NFNS, Age Group, VRNF, EK3-2, Sequencing, neuroglial neoplasm, erk, Gemistocytic, l(3)07825, Whole Exome, glial tumor, protein-cysteine kinase activity, Xanthoastrocytoma, Whole, Hpr kinase activity, CG17077, rll, Development and Research, STK26, NF1, NF-1, nf1, p38-2, von Reklinghausen disease, Tumors of Neuroglia, Methylations, myelin basic protein kinase activity, Sequence Analyses, Pilocytic Astrocytomas, Antemortem Diagnoses, RNA, Ets, findings, Complete Exome Sequencings, grupo, 35 kDa dystrophin-associated glycoprotein, Infants, diffuse, RNA Sequence Determinations, malignant glioma, ATR2, Polykaryocyte, stress-activated kinase activity, Truncus, MAP-2 kinase activity, BRAF1, TRT, protein serine kinase activity, Histone, Cell, SGCG, protein phosphokinase activity, truncus encephali, Exome Sequencing, ATRX, PKA, Cerebrus, PKC, stress-activated protein kinase activity, mapk2, mapk1, pnt-P1, pnt-P2, INSDC_feature:regulatory, Giant, protein kinase p58 activity, serine/threonine protein kinase activity, Nondeletion type, CG12559, Grade I, DMDA1, Neuroglial Neoplasms, Glial Cell, dpERK1, Intracranial Astrocytomas, Truncus Cerebrus, Von Recklinghausen disease, Childhood, dsk1, Histone H1(s), Bevacizumab-awwb, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, DXHXS6677E, Hp1bp2, Rad54, dpMAPK, Braf2, Mixed Oligoastrocytoma, quotient, Malignant Gliomas, RAD54, biopsy, Fibrillary Astrocytoma, protein serine-threonine kinase activity, POINT, SAP kinase activity, CG8705, Giant Cells, Glioma 1, glycogen synthase kinase activity, MGC130048, Antemortem Diagnosis, Brainstem, protein kinase A activity, Activity, no ICD-O subtype" EXACT [SNOMEDCT_2005_07_31:74532006], glial tumors, Mpk2, DmelCG17077, histology, p42mapk, Pnt, tumour of the neuroglia, Astrocytomas, Intervention Study., SR2-1, Truncus Cerebri, Classifications, Multinucleated, Histone H2b, Histone H2a, hierarchies, png, [M]Glioma NOS (morphologic abnormality), XLMR hypotonic face syndrome, Grade II Astrocytomas, AI314845, hEST2, DKCB4, kinase-related transforming protein, mitogen-activated protein kinase activity, cytopathology, Alpha-thalassemia-X-linked intellectual disability syndrome, anatomy and histology, mpk1, "glioma, Pnt-P1, Gemistocytic Astrocytoma, Group, Erk/Map kinase, Determination, DKCA2, Rests, Complete Exome Sequencing, neuroglial tumour, Whole Transcriptome Sequencing, DERK-A, type 1 neurofibromatosis, E(sina)7, Rl, free, Raf kinase activity, H3.3A, 9930012E13Rik, MP kinase activity, serine kinase activity, DERK, C230098H17, atypical protein kinase C activity, Pathologies, Astroglioma, MBP kinase II activity, gamma-sarcoglycan, mitogen-activated S6 kinase activity, protein-aspartyl kinase activity, dERK, D6Ertd631e, Research Priority, glioma, neoplasm of the neuroglia, infrequent, TR, ATR, Glioma (except Nasal glioma, B-RAF1, MAP kinase 2 activity, wide/broad, Oligoastrocytoma, Mapk, IDH, SG-gamma, Astrocytic, CG8318, Erk1, ERK1, D-Ets-2, obsolete_glioma, IDP, ERK2, mapk1a, ets94F, 0123/09, grade 1, Syncytia, IDCD, Determinations, M phase-specific cdc2 kinase activity, Taxonomies, Screenings, XBR, mapk1b, MapK, MAPK, Examinations and Diagnoses, Avastin, Alpha-thalassemia/mental retardation syndrome, Gliomas, brain stem, Glial Cell Tumor, Postmortem Diagnosis, ATRX syndrome, serine protein kinase activity, dNF1, erk2, mapk, M line, Diagnoses and Examination, ERKa, phosphorylase B kinase kinase activity, Postmortem Diagnoses, RAFB1, histopathology, Anaplastic Astrocytoma, BcDNA:RE08694, protein glutamyl kinase activity, Review, l(2R)EMS45-39, MRXHF1, Childhood Cerebral, AA387315, DmelCG12559, p38, Protoplasmic Astrocytoma, RAD54L, gamma (35kDa dystrophin-associated glycoprotein), DpErk, DpERK, ptd, Intracranial, ErkA, PntP2, ERKA, hydroxyalkyl-protein kinase activity, wide, "malignant Neuroglial tumor" EXACT [NCI2004_11_17:C4822], WEE1Hu, DMDA, Patient, Tumor of the Neuroglia, PntP1, epsilon PKC, E(E2F)3D, glial tumour, grade I, PNTP2, Review of Reported Cases, H3F3, Fibrillary Astrocytomas, Transcriptome Sequencings, PNTP1, pERK, Gruppe, "malignant glioma - category" EXACT [SNOMEDCT_2005_07_31:416500007], ribosomal S6 protein kinase activity, calcium/phospholipid-dependent protein kinase activity, Grade II, SGCG_HUMAN, low grade, GroupII, Complete Exome, taxonomy, ETS2, low frequency, Ets2, NS7, broad, neurofibromatosis, Malignant, TYPE, lamina medullaris incompleta pallidi, 4833408C14Rik, DAGA4, pntegfr, 0608/07, nondeletion type, HP1-BP38, 35DAG, frontal gland, Mass, SFM1, serine(threonine) protein kinase activity, NRSF, PXA, Mixed Gliomas, SCG3, HEL-216, AI788952, Cerebral, T-antigen kinase activity, h3.3a, galactosyltransferase-associated kinase activity, h3.3b, XH2, WES, Taxonomy, Diversity, hgg, Research, xp42, Intracranial Astrocytoma, Childhood Cerebral Astrocytomas, E030024J03Rik, Anaplastic Astrocytomas, p42 mitogen-activated protein kinase activity, CG18732, Juvenile Pilocytic, ATP:protein phosphotransferase (MAPKK-activated) activity, dye terminator sequencing, Grade III Astrocytoma, "malignant glioma (morphologic abnormality)" EXACT [SNOMEDCT_2005_07_31:269505000], protein kinase (phosphorylating) activity, AI447451, RNA Sequence Analyses, CMM9, Raf-1, grupos, time of survival, Clients, JMS, RNA Sequencing, DmERK-A, [M]Gliomas, casein kinase (phosphorylating) activity, HHT1, l(3)j1B7, Astrocytic Gliomas, Grade III, Childhood Cerebral Astrocytoma, ert1, Edg, malignant, prkm2, prkm1, CT39192, 2610008J04Rik, TelN, Astrogliomas, Bevacizumab awwb, Juvenile Pilocytic Astrocytomas, brainstem, Client, Examination and Diagnoses, Pleomorphic, neoplasm of neuroglia, LGMD2C, group, Juvenile, Alpha-thalassemia/intellectual disability syndrome, neurofibromatosis type 1 microdeletion syndrome, p38delta, Brain Stems, twitchin kinase activity, Priority, survival, Review Literature, Mass Screenings, EST2, AP50 kinase activity, Research Activities, HEL-S-26, Pleomorphic Xanthoastrocytoma, MBP kinase I activity, Syncytium, Multinucleated Giant Cell, B-raf, Mixed, [M]Glioma NOS, methylation, truncus encephalicus, Neuroglial tumor, l(3)s118306, Xp42, Glial Tumor, threonine-specific protein kinase activity, NOS (except Nasal glioma, Complete Transcriptome Sequencing, Neuroglial Neoplasm, mitogen activated kinase activity, pleomorphic Xantho-astrocytoma, Su(Raf)2B, Malignant glioma, Polykaryocytes, Rest, Astrocytic Glioma, EY2-2, Brainstems, sample population, Biological Diversity, h3.3, tumor of neuroglia, Neoplasm of Neuroglia, Ets58AB, D-ERK, no ICD-O subtype, PFBMFT1, Braf-2, Alpha-thalassemia X-linked intellectual disability syndrome, RNA Sequence Analysis, cardinality, SCARMD2, Glial Cell Tumors, AW494271, ResT, ORW1, groupe, MAP kinase 1 activity, A-kinase activityfalseGenomic profiling of paediatric high grade gliomas from the HERBY clinical trialThe HERBY trial was a phase-II open-label, randomised, multicentre trial evaluating bevacizumab in patients with newly-diagnosed non-brainstem high grade glioma (HGG) between the ages of 3-18yrs. 121 patients were randomised with 1yr event-free survival as the primary end-point. Confirmation of HGG diagnosis by reference pathology was mandatory before randomisation, followed by review with five independent expert neuropathologists. We collected specimens from 89 patients consenting to translational research, and performed Sanger sequencing for H3F3A, Illumina 450K BeadArray methylation profiling, and whole exome sequencing and RNA sequencing where possible. 7/89 patients (8%) harboured H3F3A G34R/V mutations, whilst 24/89 (27%) harboured H3F3A K27M, the latter reflecting a high proportion of the novel entity recognised in the 2016 WHO classification of diffuse midline glioma with H3K27M mutation. Both histone mutations conferred a significantly shorter progression-free (p=0.0104) and overall survival (p=0.00159). 450K methylation subtyping additionally identified a number of subgroups in histone wild-type cases. These included infrequent (4/86, 4.6%) cases with IDH1 mutation in older children, further categorised into astrocytic ATRX-mutant (n=3) or 1p19q co-deleted with TERT promoter mutation (n=1). 9/74, (12%) of cases were classified as biologically resembling pleomorphic xanthoastrocytoma (PXA) by methylation profiling, with 5/9 harbouring BRAF V600E mutations and epithelioid histology, and 3/9 NF1 mutation and giant cell features. Three cases had methylation profiles more closely resembling low grade gliomas, though were morphologically high grade, and harboured MAPK dysregulation in two cases, with the third part of an additional infant (<3yrs) cohort. Finally, four cases had a mutational burden several orders of magnitude higher than the rest, with (2197-5332) somatic coding variants/sample reflecting a hypermutator phenotype. These data provide an important insight into the wide biological diversity of ‘HGG’ found in the paediatric age group and allow for a profound refinement of clinical trial interpretation.2018-05-14 21:51:06EGAS000010023289606EGAD00001004070EGAD00001004036EGAC00001000384