Disruption of ataxia telangiectasia-mutated kinase enhances radiation therapy efficacy in spatially directed diffuse midline glioma models.

doi:10.1172/JCI179395

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Article

Disruption of ataxia telangiectasia-mutated kinase enhances radiation therapy efficacy in spatially directed diffuse midline glioma models.

The Journal of clinical investigation - 16 Jun 2025

Mangoli Avani, Valentine Vennesa, Maingi Spencer M, Wu Sophie R, Liu Harrison Q, Aksu Michael, Jain Vaibhav, Foreman Bronwen E, Regal Joshua A, Weidenhammer Loren B, Stewart Connor E, Guerra Garcia Maria E, Hocke Emily, Abramson Karen, Michaeli Tal Falick, Williams Nerissa T, Luo Lixia, Romero Megan, Deland Katherine, Gadd Samantha, Uchida Eita, Attardi Laura, Abe Kouki, Hashizume Rintaro, Ashley David M, Becher Oren J, Kirsch David G, Gregory Simon G, Reitman Zachary J

Abstract excerpt

Diffuse midline gliomas (DMGs) are lethal brain tumors characterized by p53-inactivating mutations and oncohistone H3.3K27M mutations that rewire the cellular response to genotoxic stress. We used RCAS/tv-a retroviruses and Cre recombinase to inactivate p53 and induce native H3.3K27M mutations in a lineage- and spatially directed manner. We generated primary mouse tumors that recapitulated human DMG. Disrupting...

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PMID: 40244686
DOI: 10.1172/JCI179395
PMCID: PMC12165813

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