biostudies-literatureNuechterlein NNational Institute of Neurological Disorders and StrokeNational Science Foundation Graduate Research Fellowship ProgramNINDS NIH HHSNCI NIH HHS41https://www.ebi.ac.uk/biostudies/studies/S-EPMC11390787biostudies-literatureUnknown148(1)Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e-5) and the CGGA (p = 0.03, p < 1e-3). HOXD12 gene body hypermethylation was associated with older age, higher WHO grade, and shorter survival in the TCGA (p < 1e-6, p < 0.001, p < 1e-3) and with older age and higher WHO grade in Capper et al. (p < 0.002, p = 0.014). In the TCGA, HOXD12 gene body hypermethylation and elevated expression were indepActa neuropathologicaHOXD12 defines an age-related aggressive subtype of oligodendroglioma.PMC11390787R35 CA253119DGE-1762114Intramural Research ProgramGilbert MRMcGranahan TRajan SNuechterlein NShelbourn AAldape KShapiro LGHolland ECHa VCimino SArora SCimino PJfalseHOXD12 defines an age-related aggressive subtype of oligodendroglioma.Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e-5) and the CGGA (p = 0.03, p < 1e-3). HOXD12 gene body hypermethylation was associated with older age, higher WHO grade, and shorter survival in the TCGA (p < 1e-6, p < 0.001, p < 1e-3) and with older age and higher WHO grade in Capper et al. (p < 0.002, p = 0.014). In the TCGA, HOXD12 gene body hypermethylation and elevated expression were indep2024-01-01T00:00:00Z2024 Sep2026-06-02T23:22:34.551Z2025-04-04T07:41:06.93ZS-EPMC113907873925941410.1007/s00401-024-02802-1