ArticleNeuro-oncology2023
Integrated molecular analysis reveals hypermethylation and overexpression of HOX genes to be poor prognosticators in isocitrate dehydrogenase mutant glioma.
Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas.Cell reports. Medicine · 2026Article
- Integrative multi-omics analysis decodes HOXC9-driven malignant transformation and metastasis in OSCC.iScience · 2025Article
- Integration of Multi-omics Data Based on Deep Learning for Subtyping of Low-Grade Glioma.Journal of molecular neuroscience : MN · 2025Article
- Oligosarcoma uniformly exhibits a HOX gene family hypermethylation signature.Acta neuropathologica · 2025Article
- The molecular history of IDH-mutant astrocytomas without adjuvant treatment.Brain pathology (Zurich, Switzerland) · 2025Article
- Contrast-enhanced ultrasound can differentiate the level of glioma infiltration and correlate it with biological behavior: a study based on local pathology.Journal of ultrasound · 2025Article
- IDH mutant high-grade gliomas.Frontiers in molecular neuroscience · 2025Review
- Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- [A two-site combined prediction model based on HOXA9 DNA methylation for early screening of risks of meningioma progression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Epigenetic landscape reorganisation and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma.Acta neuropathologica · 2024Article
- The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?Neuro-oncology · 2024Review
- Hoxc10-mediated 'positional memory' regulates cartilage formation subsequent to femoral heterotopic grafting.Journal of cellular and molecular medicine · 2024Article
- HOXD12 defines an age-related aggressive subtype of oligodendroglioma.Acta neuropathologica · 2024Article
- Prognostic value of integrative genomic approaches for IDH-mutant gliomas.Neuro-oncology · 2023Article
- Intercellular adhesion molecule 1 links glioblastoma biology to a scalable prognostic model integrating clinical, imaging, and molecular features.Neuro-oncology advancesArticle
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundDiffuse gliomas represent over 80% of malignant brain tumors ranging from low-grade to aggressive high-grade lesions. Within isocitrate dehydrogenase (IDH)-mutant gliomas, there is a high variability in survival and a need to more accurately predict outcome.
methodsTo identify and characterize a predictive signature of outcome in gliomas, we utilized an integrative molecular analysis (using methylation, mRNA, copy number variation (CNV), and mutation data), analyzing a total of 729 IDH-mutant samples including a test set of 99 from University Health Network (UHN) and 2 validation cohorts including the German Cancer Research Center (DKFZ) and The Cancer Genome Atlas (TCGA).
resultsCox regression analysis of methylation data from the UHN cohort identified CpG-based signatures that split the glioma cohort into 2 prognostic groups strongly predicting survival that were validated using 2 independent cohorts from TCGA and DKFZ (all P-values < .0001). The methylation signatures that predicted poor outcomes also exhibited high CNV instability and hypermethylation of HOX gene probes. Integrated multi-platform analyses using mRNA and methylation (iRM) showed that parallel HOX gene overexpression and simultaneous hypermethylation were significantly associated with increased mutational load, high aneuploidy, and worse survival (P-value < .0001). A 7-HOX gene signature was developed and validated using the most significantly associated HOX genes with patient outcome in both 1p/19q codeleted and non-codeleted IDHmut gliomas.
conclusionsHOX gene methylation and expression provide important prognostic information in IDH-mutant gliomas that are not captured by current molecular diagnostics. A 7-HOX gene signature of outcome shows significant survival differences in both 1p/19q codeleted and non-codeleted IDH-mutant gliomas.
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