ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/007/SRR5280317/SRR5280317_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/006/SRR5280316/SRR5280316_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/002/SRR5280322/SRR5280322_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/001/SRR5280321/SRR5280321_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/009/SRR5280319/SRR5280319_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/000/SRR5280320/SRR5280320_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/002/SRR5280312/SRR5280312_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/001/SRR5280311/SRR5280311_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/009/SRR5280319/SRR5280319_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/008/SRR5280318/SRR5280318_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/002/SRR5280322/SRR5280322_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/003/SRR5280313/SRR5280313_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/004/SRR5280314/SRR5280314_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/002/SRR5280312/SRR5280312_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/001/SRR5280321/SRR5280321_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/001/SRR5280311/SRR5280311_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/000/SRR5280320/SRR5280320_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/005/SRR5280315/SRR5280315_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/003/SRR5280313/SRR5280313_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/006/SRR5280316/SRR5280316_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/008/SRR5280318/SRR5280318_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/004/SRR5280314/SRR5280314_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/005/SRR5280315/SRR5280315_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR528/007/SRR5280317/SRR5280317_1.fastq.gzprimaryOK200GenomicsJabado Lab, Department of Pediatrics, McGill Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA376547Homo sapiensGain-of-function mutations in histone 3 (H3) variants are found in a large proportion of pediatric high-grade gliomas (pHGG) and are often associated with p53 loss and PDGFRA amplification. However, a lack of faithful models has hampered investigation of disease mechanisms and preclinical development. Here, we describe a somatic mouse model of H3.3K27M-driven HGG, which faithfully recapitulates human H3.3K27M pHGG. H3.3K27M and p53 loss are sufficient for neoplastic transformation but only within a specific window of brain development. In this model, H3.3K27M primes the PDGFRA pathway during transformation, and accordingly gain of wild-type PDGFRA decreases latency and increases invasion. Finally, we reveal a previously underappreciated dynamic regulation of H3K27 trimethylation at specific loci. Overall, this experimental model provides key insights into oncohistone-driven pHGG pathogenesis and will enable investigations of future therapies. Overall design: We performed genome-wide transcriptome profiling (RNAseq) of 12 samples derived from human patients: matched normal brain controls (normal brain tissue from pediatric brain tumor patients n = 3), pediatric high-grade gliomas (pHGG) that are wild-type for H3.3 and TP53 (n = 4), pHGG with H3.3K27M and loss-of-function TP53 mutations (n = 5).xref:PubMed:29107533ENAbeta[[3]]-Tub, DmelCG17117, dp53, human being, p50, Laboratory, p53, Mus domesticus, 143391_i_at, RNA-seq., beta3 TU, LFS1, betaTub3, House Mouse, Tp53, l(3)05745, Human, DMP53, Homo sapiens, House, bbl, Mus musculus domesticus, Whole Transcriptome Shotgun Sequencing, Dmp53, anon-EST:Liang-2.13, Mice, Man, AI115593, 1323/07, clone 2.13, Man (Taxonomy), BCC7, APDGFR, Swiss, D.m.BETA-60D, beta-Tub6D, PDGFR2, dmp53, T, DmP53, 1422/04, Swiss Mice, CD140a, RHEPDGFRA, B3t, DmelCG3401, Trp53, Dp53, betaTub60C, beta3-tubulin, beta[[3]]-tubulin, TRP53, house mouse, CG17117, CD140A, p50/tubulin, beta-Tub60D, CG10873, Dmbeta3, Dm-HTH, BETA 60D, Modern, prac, beta3t, beta3-Tub, mouse, Cell, Xp53, 3t, Mus, p53/tubulin, bfy, PDGFACE, Pdgfr-2, beta[[3]] tubulin, Tub60D, HTH, Hth, Embryonic, PDGFR-2, CG33336, Mus musculus, beta-tub, mice, DmelCG33336, D-p53, Swiss Mouse, beta60C, CG3401, beta3Tub, beta3TUB, Dm-P53, l(3)86Ca, House Mice, beta3, dtl, human, domesticus, Laboratory Mice, Tub, DTB3, Meis1, hth1, hth2, betatub60D, Modern Man, P53, p44, bhy, Mouse, CG31325, Laboratory Mouse, betaTubHuman, Modern., human being, Man (Taxonomy), Homo sapiens, man, Man, human, Modern ManfalseHomo sapiensH3.3K27M cooperates with p53 loss and Pdgfra gain in mouse embryonic neural progenitor cells to induce invasive high-grade gliomas [Human RNA-Seq]2025-09-242017-10-29PRJNA376547GSE95277960629107533