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 journalArticle

24 Citations (Scopus)

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

Fingerprint

Glioma
Methylation
Glioblastoma
Epigenomics
Genes
Neoplasms
Biomarkers
Survival
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma : Association with tumor WHO grade and clinical outcome. / Vinci, Angela Di; Casciano, Ida; Marasco, Elena; Banelli, Barbara; Ravetti, Gian Luigi; Borzì, Luana; Brigati, Claudio; Forlani, Alessandra; Dorcaratto, Alessandra; Allemanni, Giorgio; Zona, Gianluigi; Spaziante, Renato; Gohlke, Henning; Gardin, Giovanni; Merlo, Domenico Franco; Mantovani, Vilma; Romani, Massimo.

In: Journal of Cancer Research and Clinical Oncology, Vol. 138, No. 1, 01.2012, p. 35-47.

Research output: Contribution to journalArticle

Vinci, AD, Casciano, I, Marasco, E, Banelli, B, Ravetti, GL, Borzì, L, Brigati, C, Forlani, A, Dorcaratto, A, Allemanni, G, Zona, G, Spaziante, R, Gohlke, H, Gardin, G, Merlo, DF, Mantovani, V & Romani, M 2012, 'Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: Association with tumor WHO grade and clinical outcome', Journal of Cancer Research and Clinical Oncology, vol. 138, no. 1, pp. 35-47. https://doi.org/10.1007/s00432-011-1070-5
Vinci, Angela Di ; Casciano, Ida ; Marasco, Elena ; Banelli, Barbara ; Ravetti, Gian Luigi ; Borzì, Luana ; Brigati, Claudio ; Forlani, Alessandra ; Dorcaratto, Alessandra ; Allemanni, Giorgio ; Zona, Gianluigi ; Spaziante, Renato ; Gohlke, Henning ; Gardin, Giovanni ; Merlo, Domenico Franco ; Mantovani, Vilma ; Romani, Massimo. / Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma : Association with tumor WHO grade and clinical outcome. In: Journal of Cancer Research and Clinical Oncology. 2012 ; Vol. 138, No. 1. pp. 35-47.
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AU - Vinci, Angela Di

AU - Casciano, Ida

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AU - Banelli, Barbara

AU - Ravetti, Gian Luigi

AU - Borzì, Luana

AU - Brigati, Claudio

AU - Forlani, Alessandra

AU - Dorcaratto, Alessandra

AU - Allemanni, Giorgio

AU - Zona, Gianluigi

AU - Spaziante, Renato

AU - Gohlke, Henning

AU - Gardin, Giovanni

AU - Merlo, Domenico Franco

AU - Mantovani, Vilma

AU - Romani, Massimo

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N2 - 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.

AB - 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.

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