Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: Association with tumor WHO grade and clinical outcome

Angela Di Vinci, Ida Casciano, Elena Marasco, Barbara Banelli, Gian Luigi Ravetti, Luana Borzì, Claudio Brigati, Alessandra Forlani, Alessandra Dorcaratto, Giorgio Allemanni, Gianluigi Zona, Renato Spaziante, Henning Gohlke, Giovanni Gardin, Domenico Franco Merlo, Vilma Mantovani, Massimo Romani

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics. Methods Weevaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing. Results We demonstrated the direct statistical correlation between the level ofmethylation of allHOXA genes examined andWHOgrading.Moreover, in glioblastoma patients, higher level of HOXA9 and HOXA10 methylation significantly correlated with increased survival probability (HOXA9-HR: 0.36, P = 0.007;HOXA10-HR: 0.46, P = 0.045; combined HOXA9 and 10-HR 0.28, P = 0.004). Conclusions This study identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma patients. Our data indicate that these epigenetic changes may be biomarkers of clinically different subgroups of glioma patients that could eventually benefit from personalized therapeutic strategies.

Original languageEnglish
Pages (from-to)35-47
Number of pages13
JournalJournal of Cancer Research and Clinical Oncology
Volume138
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • DNA methylation
  • Epigenetics
  • Glioma
  • HOXA genes
  • Mass ARRAY
  • Pyrosequencing

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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