ArticleMolecular oncology2021
Widespread overexpression from the four DNA hypermethylated HOX clusters in aggressive (IDHwt) glioma is associated with H3K27me3 depletion and alternative promoter usage.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Homeobox genes in endocrine tumorigenesis: mechanisms, tumor microenvironment interaction, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas.Cell reports. Medicine · 2026Article
- TERT promoter methylation predicts overall survival, immune cell infiltration and response to immunotherapy in clear cell renal cell carcinoma.Clinical epigenetics · 2025Article
- HOX gene dysregulation in glioblastoma: a narrative review of current advances.Discover oncology · 2025Review
- Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.Laboratory investigation; a journal of technical methods and pathology · 2024Article
- Epigenetic landscape reorganisation and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma.Acta neuropathologica · 2024Article
- HOXD12 defines an age-related aggressive subtype of oligodendroglioma.Acta neuropathologica · 2024Article
- Association of RAN and RANBP2 Gene Polymorphisms With Glioma Susceptibility in Chinese Children.Cancer reports (Hoboken, N.J.) · 2024Article
- Integrated molecular analysis reveals hypermethylation and overexpression of HOX genes to be poor prognosticators in isocitrate dehydrogenase mutant glioma.Neuro-oncology · 2023Article
- Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes.Scientific reports · 2023Article
- Article
- L1 chimeric transcripts are expressed in healthy brain and their deregulation in glioma follows that of their host locus.Human molecular genetics · 2022Article
- Article
- The Long Non-Coding RNAInternational journal of molecular sciences · 2022Article
- Bivalent Regulation and Related Mechanisms of H3K4/27/9me3 in Stem Cells.Stem cell reviews and reports · 2022Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- HOX gene regulation in glioma stem cells, mediators of resistance in breast cancer, and paradoxical therapeutic interventions.Molecular oncology · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In human, the 39 coding HOX genes and 18 referenced noncoding antisense transcripts are arranged in four genomic clusters named HOXA, B, C, and D. This highly conserved family belongs to the homeobox class of genes that encode transcription factors required for normal development. Therefore, HOX gene deregulation might contribute to the development of many cancer types. Here, we study HOX gene deregulation in adult glioma, a common type of primary brain tumor. We performed extensive molecular analysis of tumor samples, classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found widespread expression of sense and antisense HOX transcripts only in aggressive (IDHwt) glioma samples, although the four HOX clusters displayed DNA hypermethylation. Integrative analysis of expression, DNA methylation, and histone modification signatures along the clusters revealed that HOX gene upregulation relies on canonical and alternative bivalent CpG island promoters that escape hypermethylation. H3K27me3 loss at these promoters emerges as the main cause of widespread HOX gene upregulation in IDHwt glioma cell lines and tumors. Our study provides the first comprehensive description of the epigenetic changes at HOX clusters and their contribution to the transcriptional changes observed in adult glioma. It also identified putative 'master' HOX proteins that might contribute to the tumorigenic potential of glioma stem cells.
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