EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001001437EGAEGA study EGAS00001001437KNS42 and SF188 H3K36me3 chipSeqEGArestrictedHITS-CLIP, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, glial cell tumor, "malignant glioma - category" EXACT [SNOMEDCT_2005_07_31:416500007], ChIP-Chip, Chromatin Immuno-precipitation, no ICD-O subtype" EXACT [SNOMEDCT_2005_07_31:74532006], malignant glioma, malignant, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, neuroglial tumor, Genome Sequencing, Cell Lines, ChIP Sequencing, CLIP-Seq, Assay for Transposase-Accessible Chromatin Using Sequencing, ChIP-PET, h3f3a, Cell, ChIP-Exo, Mutations, Complete Genome, malignant Neuroglial tumor, Chromatin Immunoprecipitation Sequencing-Chip, Line, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, malignant" EXACT [SNOMEDCT_2005_07_31:189909006], "glioma, Neuroglial tumor, H3.3A., ChIA-PET, Lines, h3.3a, Chromatin, Immunoprecipitation, Chromatin Immunoprecipitation Sequencing Chip, h3.3b, Chromatin Immuno precipitation Sequencing, Complete, Whole Genome, ChIP, Chromatin Immunoprecipitation Paired End Tag, Chromatin Immuno Precipitation Paired End Tag, neuroglial tumour, Complete Genome Sequencing, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, Chromatin Immunoprecipitation, Chromatin Immuno-precipitation Sequencing, ChIP Exonuclease, ChIP-Seq, Sequencing, Assay for Transposase Accessible Chromatin Using Sequencing, Chromatin Immunoprecipitation Paired-End Tag, h3.3, "malignant glioma (morphologic abnormality)" EXACT [SNOMEDCT_2005_07_31:269505000], "malignant Neuroglial tumor" EXACT [NCI2004_11_17:C4822], Whole, Chromatin Immuno-Precipitation Paired-End Tag, ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, glioma, H3F3, ChIP-ExonucleaseMGC130048, Par1c, Materials, Sequence Determination, mycna, A4, mycnb, K25C, protein, CK-27, Astrocytomas, DmelCG8201, Social Controls, Mutations, dmTAF[[II]]230, Histone H2b, School-Age, Histone H2a, type I Ha6, Analysis, protein aggregate, Formal Social Controls, adult, IKKg, ChIA-PET, KEY, Key, gamma sarcoglycan, Chromatin Immunoprecipitation Sequencing Chip, Chromatin Immuno precipitation Sequencing, Forebrain, TFIID TAF250, Genomes, Analyses, Determination, cel, ChIP, FATE, Chromatin Immuno Precipitation Paired End Tag, Nmyc1, Giant Cell Glioblastoma, N-myc, Sequence Determinations, Astrocytoma, H3.3A, Social, Chromatin Immunoprecipitation Paired-End Tag, DNA Sequence Analysis, HRa-1, XN-myc, grade IV adult Astrocytic tumor, Type I keratin 48 kDa, ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, Histone H5, Histone H4, gamma-sarcoglycan, Histone H7, transcription from bacterial-type RNA polymerase promoter, CG16701, Histone H1, Histone H3, distinct from, close to, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, dTAF[[II]]230, CG8201, Type I keratin KA40, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, SG-gamma, Genome Sequencing, Forebrains, TAF200, dMARK, Giant Cell, TAFII-250, TAF250/230, ChIP-PET, CG11960, Determinations, CG30131, Programs, CG30132, EMK, DmIKKgamma, TAFII250, Complete Genome, dIKK, primary glioblastoma multiforme, School Age, DPAR-1, Kenny, DNA Sequence Determinations, CT43, Genetic Materials, sarcoglycan, median, DNA Sequence, Hair keratin, Adults, Genetic Material, FB, DNA sequencing, xN-myc1, Populations, Glioblastoma, Drives, death rate, spongioblastoma multiforme, IKK-gamma, Control, GBM, INSDC_feature:gene, whole genome, ChIP Exonuclease, Controls, gamma (35kDa dystrophin-associated glycoprotein), CG17603, Children, Krt1-5, TAF[[II]], Krt1-22, l(2)27C1, DMDA, DmelCG16910, Grade IV Astrocytomas, Taf250, Patient, Material, BcDNA:RH48823, 35kD dystrophin-associated glycoprotein, SR3-5, bacterial transcription, MARK, Cistron, School-Age Population, DNA, H3F3, Regulation, ChIP-Exonuclease, Keratin-5, TAF230, Regulations, ChIP-Chip, d230, SGCG_HUMAN, Chromatin Immuno-precipitation, Nmyc, ODED, Par-1c, number, Gene, CLIP-Seq, dTAFII250, Assay for Transposase-Accessible Chromatin Using Sequencing, Grade IV, protein-containing complex, Keratin complex-1, h3f3a, EfW1, presence, dIKK-gamma, TYPE, DAGA4, mycn, dmTAF1, dPAR-1, Taf230, DmIKK-gamma, NMYC, Chromatin Immunoprecipitation Sequencing-Chip, 35DAG, Gene Products, dmIKKgamma, IKK[[gamma]], dPar-1, MAM, gamma-SG, Giant Cell Glioblastomas, SCG3, nmyc, Histone H3.3, TAF250, h3.3a, School-Age Populations, Immunoprecipitation, h3.3b, 27C1, Taf200, Complete, Whole Genome, dTAF[[II]]250, Genetic, grade IV adult astrocytic tumor, cell, Chromatin Immunoprecipitation Paired End Tag, l(2)k06323, ligand, Cytokeratin-27, Complete Genome Sequencing, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, Taf1p, Population, Nmuc1, Sequencing, dTAF250, Glioblastoma Multiforme, PAR-1, MODED, IKK, time of survival, Clients, Whole, Par-1, Keratin-36, Type I inner root sheath-specific keratin-K25irs3, Grade IV Astrocytoma, bHLHe37, School Age Population, TAF, Methylations, XNmyc, Sequence Analyses, HITS-CLIP, grade IV adult astrocytic tumour, par1, TAF[[II]]250, 35 kDa dystrophin-associated glycoprotein, Formal Social Control, Keratin-25C, protein complex, Keratin-27, Proteins, dPAR1, ChIP Sequencing, dPar1, l(3)84Ab, BG:DS00004.13, Cistrons, Histone, Client, Cell, ChIP-Exo, SGCG, LGMD2C, dTAF230, near to, IKKgamma, adult glioblastoma multiforme, count in organism, survival, native protein, Social Control, p230, DNA Sequencing, anon-WO0210402.19, c-nmyc, Protein, TAF[[II]]250/230, TFIID, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, methylation, acidic, glioblastoma multiforme, Taf[[II]]250, Chromatin, prosencephalon, TAF[[II]]230, DMDA1, distinct, Protein., Dmikkgamma, MHRa-1, K27, Glioblastomas, Chromatin Immunoprecipitation, Chromatin Immuno-precipitation Sequencing, TAF[II]250, patient, CG16910, ChIP-Seq, Histone H1(s), School Age Populations, Assay for Transposase Accessible Chromatin Using Sequencing, DNA Sequence Determination, Nmyc-1, h3.3, Protein Gene Products, Gene Proteins, DNA Sequence Analyses, DmelCG17603, approaches, Chromatin Immuno-Precipitation Paired-End Tag, vicinity of, SCARMD2, cardinality, K36, DPar1, H3(any), regulation, PAR1, Par1, gene C29, hypothesis, TAF1falseChromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in paediatric high grade glioma cell lines KKNS4 and SF188 with and without a G34V mutation in H3F3AGlioblastomas of children and young adults have a median survival of only 12-15months and are clinically and biologically distinct from histologically similar cancers in older adults1. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A2, occurring either at or close to key residues marked by methylation for regulation of transcription – K27 and G34. We performed chromatin immunoprecipitation linked to next-generation whole genome sequencing (ChIP-Seq) for H3K36me3 in order to test the hypothesis that, rather than total H3K36me3, the G34V mutation may instead result in differential binding of the trimethyl mark throughout the genome. Compared with H3F3A wild-type SF188 paediatric GBM cells, H3K36me3 was found to be significantly differentially bound in KNS42 cells at 5130 distinct regions of the genome corresponding to 156 genes. Concurrent whole genome DNA sequencing demonstrated that this was not confounded by copy number alterations. The cerebral hemispheric-specific G34 mutation drives a distinct expression signature through differential genomic binding of the K36 trimethylation mark (H3K36me3). The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem cell maintenance, cell fate decisions and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene which is causative of glioblastomas when expressed in the correct developmental context. This driving aberration is selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein.2021-07-05 12:57:53EGAS000010014379606EGAD00001004119EGAC00001000384