{"doi":"10.1007/s00401-024-02802-1","title":"HOXD12 defines an age-related aggressive subtype of oligodendroglioma","abstract":"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 independently prognostic of NOTCH1 and PIK3CA mutations, loss of 15q, MYC activation, and standard histopathological features. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue, particularly within cycling and OPC-like cells, and was associated with a stem-like phenotype. A pan-HOX DNA methylation analysis revealed an age and survival-associated HOX-high signature that was tightly associated with HOXD12 gene body methylation. Overall, HOXD12 expression and gene body hypermethylation were associated with an older, atypically aggressive subtype of oligodendroglioma.","journal":"Acta Neuropathologica","year":2024,"id":447457,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1265521,"name":"Sadie Cimino","orcid":null,"position":1,"is_corresponding":false},{"id":1106322,"name":"Allison Shelbourn","orcid":null,"position":2,"is_corresponding":false},{"id":1265522,"name":"Vinny Ha","orcid":null,"position":3,"is_corresponding":false},{"id":311198,"name":"Sonali Arora","orcid":"0000-0002-6661-3024","position":4,"is_corresponding":false},{"id":349611,"name":"Sharika Rajan","orcid":null,"position":5,"is_corresponding":false},{"id":428152,"name":"Linda G. Shapiro","orcid":"0000-0002-9495-0968","position":6,"is_corresponding":false},{"id":226433,"name":"Eric C. Holland","orcid":"0000-0002-3792-7120","position":7,"is_corresponding":false},{"id":13200,"name":"Kenneth Aldape","orcid":"0000-0001-5119-7550","position":8,"is_corresponding":false},{"id":915261,"name":"Tresa McGranahan","orcid":"0000-0003-0472-4252","position":9,"is_corresponding":false},{"id":109755,"name":"Mark R. Gilbert","orcid":"0000-0003-2556-9722","position":10,"is_corresponding":false},{"id":305856,"name":"Patrick J. Cimino","orcid":"0000-0003-0441-4502","position":11,"is_corresponding":false},{"id":732793,"name":"Nicholas Nuechterlein","orcid":"0000-0002-9599-0865","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T02:01:59.101070Z","pmid":"39259414","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}