Original ArticleHOXA7, 9, and 10 are methylation targets associated with aggressive behavior in meningiomas
Section snippets
Tumor specimens and DNA/RNA preparation
DNA was extracted from 131 consecutive frozen meningioma and 7 meningeal samples, microscopically free of disease, excised from patients who underwent operation at the Neurosurgery Branch of the IRCCS AOU San Martino – IST between 2006 and 2009. Informed consent was obtained from all patients.
Tumors, classified according to the WHO classification, included 100 WHO I, 28 WHO II, and 3 WHO III samples. Ninety-three samples were solitary meningiomas at the onset, 14 samples were recurrence of
Results and Discussion
Epigenetics, and in particular DNA methylation, is one of the mechanisms through which cancer-related genes are inappropriately silenced or reactivated. In recent years, the interest on epigenetic alterations as cancer biomarkers independent of the functional effects has steadily increased.25
To identify biomolecular parameters that are potentially useful to improve the accuracy of the diagnosis and prognosis in meningioma, we have evaluated the methylation level of HOXA3, 7, 9, and 10 by
Conclusions
The identification of biomolecular parameters that are useful to improve the classification of meningioma may optimize the indications for possible adjuvant therapies and closer follow-up. We have conducted our study on HOXA genes, whose expression or methylation is altered in central nervous system tumors, and it has been put in relation with phenotype and resistance to treatment.17, 18, 19 Our results indicate that HOXA7, 9, and 10 are methylation targets in meningioma that are able to
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HOX family transcription factors: Related signaling pathways and post-translational modifications in cancer
2020, Cellular SignallingCitation Excerpt :Post-translational modifications of HOX proteins also play a critical role in tumor progression [13–15]. Thus, studies of the regulatory mechanism of HOX proteins in tumorigenesis and development may be important for tumor diagnosis [16,17], treatment [13,18,19], and prognosis evaluation [20,21]. In this review, we highlighted the most recent findings related to HOX family transcription factors, focusing on recent developments in the understanding of HOX family transcription factor-related signaling pathways, post-translational modifications, and their roles in cancer progression.
Context-dependent HOX transcription factor function in health and disease
2020, Progress in Molecular Biology and Translational ScienceCitation Excerpt :Those listed in the Catalogue of Somatic Mutations in Cancer (COSMIC) database are plotted in Figs. 3 and 4 for HOXA9, HOXA13, HOXB1, HOXB7, HOXB9, HOXC6, HOXC8, HOXC13, and HOXD13. Mutations in homeodomain have the potential to alter its structure or DNA binding,196 although few have been verified to change function. Still more mutations are found in intrinsically disordered regions of the HOX protein outside of the homeodomain.
Molecular genetics of meningiomas
2020, Handbook of Clinical NeurologyCitation Excerpt :Some studies have leveraged the methylation status (particularly at CpG islands) to stratify and cluster these tumors according to molecular background. These efforts have associated hypermethylation at specific genes with recurrence (Kishida et al., 2012) and higher-grade lesions (Liu et al., 2005; Di Vinci et al., 2012; Gao et al., 2013), most notably the homeobox family and polycomb repressive complex 2 (PRC2) associated gene-sets. A recent study by our lab suggests that this hypermethylated phenotype may be driven in part by increased activity of the PRC2 catalytic subunit EZH2, which recruits DNA methyltransferases to these sites (Harmanci et al., 2017) (Fig. 6.5A and B).
Epigenetics, Public Health, Lifestyle, and Chemoprevention
2018, Epigenetics of Cancer PreventionGenomic and Epigenomic Landscape in Meningioma
2016, Neurosurgery Clinics of North AmericaCitation Excerpt :However, the pattern of epigenetic modification varies widely among genes and observation of hypermethylation does not necessarily translate to suppressed transcription, or conversely for hypomethylated genes (Table 3). For example, whereas ADCY3, GAS7, LAG3, LRR32, and SPON2 hypomethylation are more prominent in malignant meningiomas,57 hypermethylation of HOXA7, HOXA9, and HOXA10 are associated with high-grade meningiomas.61 Despite such heterogeneity in the epigenomic literature, several candidates have garnered interest in helping to differentiate grades II and III meningioma (see Table 3).
B. B. is the recipient of a Young Investigators Grant from the Italian Ministry of Health. This work was supported by the Italian Ministry of Health and the Regione Liguria Grant “Genetic and Epigenetic Alterations in Brain Tumors.”
The authors have read and approved the Journal policy on conflicts of interest, and they declare there are no potential conflicts of interest that could have biased the work.