HOXD12 defines an age-related aggressive subtype of oligodendroglioma.

in Acta neuropathologica by Nicholas Nuechterlein, Sadie Cimino, Allison Shelbourn, Vinny Ha, Sonali Arora, Sharika Rajan, Linda G Shapiro, Eric C Holland, Kenneth Aldape, Tresa McGranahan, Mark R Gilbert, Patrick J Cimino

TLDR

  • The study found that HOXD12 expression and gene body hypermethylation were associated with an older, atypically aggressive subtype of oligodendroglioma and may drive poorer outcomes in this subtype. The study suggests that HOXD12 expression and gene body hypermethylation may be useful as a prognostic tool for oligodendroglioma, IDH-mutant and 1p/19q-codeleted. The study's findings may have implications for the development of targeted therapies for oligodendroglioma, IDH-mutant and 1p/19q-codeleted. Future research directions could include further investigation of the role of HOXD12 expression and gene body hypermethylation in oligodendroglioma and their association with clinical features and mutations. Future research could also investigate the potential of targeting HOXD12 expression and gene body hypermethylation as a therapeutic strategy for oligodendroglioma, IDH-mutant and 1p/19q-codeleted.

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.

Overview

  • The study investigates the relationship between age and molecular alterations in oligodendroglioma, IDH-mutant and 1p/19q-codeleted. The authors found that elevated HOXD12 expression and gene body hypermethylation were associated with older patient age and shorter survival in multiple datasets. HOXD12 expression and gene body hypermethylation were also found to be independent prognostic factors for various clinical features and mutations. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue and 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. The study aims to identify age-associated molecular alterations that may drive poorer outcomes in oligodendroglioma, IDH-mutant and 1p/19q-codeleted. The primary objective of the study is to understand the role of HOXD12 expression and gene body hypermethylation in oligodendroglioma and their association with clinical features and mutations.

Comparative Analysis & Findings

  • The study compared the outcomes observed under different experimental conditions or interventions detailed in the study. The authors found that elevated HOXD12 expression and gene body hypermethylation were associated with older patient age and shorter survival in multiple datasets. HOXD12 expression and gene body hypermethylation were also found to be independent prognostic factors for various clinical features and mutations. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue and 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. The key findings of the study suggest that HOXD12 expression and gene body hypermethylation are associated with an older, atypically aggressive subtype of oligodendroglioma and may drive poorer outcomes in this subtype.

Implications and Future Directions

  • The study's findings suggest that HOXD12 expression and gene body hypermethylation are associated with an older, atypically aggressive subtype of oligodendroglioma and may drive poorer outcomes in this subtype. The study's findings also suggest that HOXD12 expression and gene body hypermethylation are independent prognostic factors for various clinical features and mutations. The study's findings may have implications for the development of targeted therapies for oligodendroglioma, IDH-mutant and 1p/19q-codeleted. Future research directions could include further investigation of the role of HOXD12 expression and gene body hypermethylation in oligodendroglioma and their association with clinical features and mutations. Future research could also investigate the potential of targeting HOXD12 expression and gene body hypermethylation as a therapeutic strategy for oligodendroglioma, IDH-mutant and 1p/19q-codeleted.
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