H3.3-G34 mutations impair DNA repair and promote cGAS/STING-mediated immune responses in pediatric high-grade glioma models.

doi:10.1172/JCI154229

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Article

H3.3-G34 mutations impair DNA repair and promote cGAS/STING-mediated immune responses in pediatric high-grade glioma models.

The Journal of clinical investigation - 15 Nov 2022

Haase Santiago, Banerjee Kaushik, Mujeeb Anzar A, Hartlage Carson S, Núñez Fernando M, Núñez Felipe J, Alghamri Mahmoud S, Kadiyala Padma, Carney Stephen, Barissi Marcus N, Taher Ayman W, Brumley Emily K, Thompson Sarah, Dreyer Justin T, Alindogan Caitlin T, Garcia-Fabiani Maria B, Comba Andrea, Venneti Sriram, Ravikumar Visweswaran, Koschmann Carl, Carcaboso Ángel M, Vinci Maria, Rao Arvind, Yu Jennifer S, Lowenstein Pedro R, Castro Maria G

Abstract excerpt

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human...

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PMID: 36125896
DOI: 10.1172/JCI154229
PMCID: PMC9663161

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