# A review of diffuse hemispheric glioma, H3 G34-mutant disease development, DNA repair, microenvironment, and treatments on the horizon **Authors:** Cameron Crowell, Ziwen Zhu, Yingxiang Li, Maria L. Varela, Quinn Ostrom, Patrick J. Cimino, Sohil H. Patel, Suzanne J. Baker, Chetan Bettegowda, Houtan Noushmehr, Claudia L. Kleinman, Laura Canty, Gustavo Alencastro Veiga Cruzeiro, Anandani Nellan, Oren Becher, Tom B. Davidson, Dolores Hambardzumyan, Adam Green, Robert Thorne, Kelli Wilson, Brett Theeler, Jason Gregory, Peter Mathen, Nadia Biassou, Sheila McThenia, Craig Erker, Robert Galvin, Ariane Soldatos, Pedro R. Lowenstein, Maria G. Castro, Sadhana Jackson PMC · DOI: 10.1038/s41698-025-01070-w · 2025-08-14 ## TL;DR This paper reviews diffuse hemispheric glioma with H3 G34 mutations, focusing on disease progression, DNA repair, and potential treatments. ## Contribution The paper synthesizes recent findings and symposium discussions to highlight new insights into H3 G34-mutant glioma biology and treatment strategies. ## Key findings - Molecular diagnostics have improved, but tumor progression mechanisms remain unclear. - DNA repair and immune microenvironment insights suggest new therapeutic opportunities. - Symposium findings highlight potential for improved survival through targeted treatments. ## Abstract Diffuse hemispheric glioma H3 G34-mutant is primarily diagnosed in adolescents/young adults. While molecular diagnostics have improved, cellular mechanisms that drive tumor progression and therapy resistance are poorly understood. Combining previous published studies with findings from the 2024 NIH G34-mutant symposium aid in summarizing translational and clinical updates on disease development, cellular repair processes, and the immune microenvironment. This collective work is meant to outline opportunities for treatment and prolonged survival. ## Full-text entities - **Genes:** PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, MUC16 (mucin 16, cell surface associated) [NCBI Gene 94025] {aka CA125}, CAMK2G (calcium/calmodulin dependent protein kinase II gamma) [NCBI Gene 818] {aka CAMK, CAMK-II, CAMKG, MRD59}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], GSX2 (GS homeobox 2) [NCBI Gene 170825] {aka DMJDS2, GSH2}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, CCND2 (cyclin D2) [NCBI Gene 894] {aka KIAK0002, MPPH3}, DNM3 (dynamin 3) [NCBI Gene 26052] {aka Dyna III}, PIM1 (Pim-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5292] {aka PIM}, CDK9 (cyclin dependent kinase 9) [NCBI Gene 1025] {aka C-2k, CDC2L4, CTK1, PITALRE, TAK}, MYCN (MYCN proto-oncogene, bHLH transcription factor) [NCBI Gene 4613] {aka FGLDS1, MODED, MPAPA, MYCNsORF, MYCNsPEP, N-myc}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, ATRX (ATRX chromatin remodeler) [NCBI Gene 546] {aka JMS, MRX52, RAD54, RAD54L, XH2, XNP}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CDK6 (cyclin dependent kinase 6) [NCBI Gene 1021] {aka MCPH12, PLSTIRE}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 115004] {aka C6orf150, D4, MB21D1, h-cGAS}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, NOTCH2NLA (notch 2 N-terminal like A) [NCBI Gene 388677] {aka N2N, NOTCH2NL}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, SETD2 (SET domain containing 2, histone lysine methyltransferase) [NCBI Gene 29072] {aka HBP231, HIF-1, HIP-1, HSPC069, HYPB, KMT3A}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, H3C2 (H3 clustered histone 2) [NCBI Gene 8358] {aka H3/l, H3FL, HIST1H3B}, DLX1 (distal-less homeobox 1) [NCBI Gene 1745], IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, FLT3LG (fms related receptor tyrosine kinase 3 ligand) [NCBI Gene 2323] {aka FL, FLG3L, FLT3L, IMD125}, OLIG2 (oligodendrocyte transcription factor 2) [NCBI Gene 10215] {aka BHLHB1, OLIGO2, PRKCBP2, RACK17, bHLHe19}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, H3-3A (H3.3 histone A) [NCBI Gene 3020] {aka BRYLIB1, H3.3A, H3F3, H3F3A}, DAXX (death domain associated protein) [NCBI Gene 1616] {aka BING2, DAP6, EAP1}, MUC17 (mucin 17, cell surface associated) [NCBI Gene 140453] {aka MUC-17, MUC-3, MUC3} - **Diseases:** seizures (MESH:D012640), neurological/cognitive abnormalities (MESH:D060825), inflammatory (MESH:D007249), Tumor (MESH:D009369), tumorigenesis (MESH:D063646), cytotoxicity (MESH:D064420), GBM (MESH:D005909), central nervous system tumors (MESH:D016543), DIPG (MESH:D000080443), Brain Tumor (MESH:D001932), tumorigenic (MESH:D002471), DHG (MESH:D005910) - **Chemicals:** steroid (MESH:D013256), salinomycin (MESH:C010327), camptothecins (MESH:D002166), abemaciclib (MESH:C000590451), TMZ (MESH:D000077204), GCV (MESH:D015774), ribociclib (MESH:C000589651), DHG (-), Infigratinib (MESH:C568950), purine (MESH:C030985) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** glycine-to-valine, glycine-to-arginine, G34, K27, G34R, K27M - **Cell lines:** H3 G34R — Mus musculus (Mouse), Hybridoma (CVCL_A0QR), H3.3 — Mus musculus (Mouse), Hybridoma (CVCL_B0EL) ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12354862/full.md --- Source: https://tomesphere.com/paper/PMC12354862