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
Original Paper

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

We evaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing.

Results

We demonstrated the direct statistical correlation between the level of methylation of all HOXA genes examined and WHO grading. 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.

Keywords

DNA methylation Epigenetics Glioma HOXA genes MassARRAY Pyrosequencing 

Supplementary material

432_2011_1070_MOESM1_ESM.pdf (3.2 mb)
Supplementary material 1 (PDF 3288 kb)
432_2011_1070_MOESM2_ESM.pdf (458 kb)
Supplementary material 2 (PDF 458 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Angela Di Vinci
    • 1
  • Ida Casciano
    • 1
  • Elena Marasco
    • 2
  • Barbara Banelli
    • 1
  • Gian Luigi Ravetti
    • 3
  • Luana Borzì
    • 1
  • Claudio Brigati
    • 1
  • Alessandra Forlani
    • 1
  • Alessandra Dorcaratto
    • 3
  • Giorgio Allemanni
    • 1
  • Gianluigi Zona
    • 4
  • Renato Spaziante
    • 4
  • Henning Gohlke
    • 5
  • Giovanni Gardin
    • 6
  • Domenico Franco Merlo
    • 7
  • Vilma Mantovani
    • 2
  • Massimo Romani
    • 1
  1. 1.Laboratory of Tumor Genetics and Epigenetics, Istituto Nazionale per la Ricerca sul CancroGenoaItaly
  2. 2.Center for Biomedical Applied Research—CRBA, University Hospital S. Orsola-MalpighiBolognaItaly
  3. 3.Department of Pathology and HistologySan Martino University HospitalGenoaItaly
  4. 4.Department of NeurosurgerySan Martino University HospitalGenoaItaly
  5. 5.Sequenom GmbHHamburgGermany
  6. 6.Medical Oncology A, Istituto Nazionale per la Ricerca sul Cancro—ISTGenoaItaly
  7. 7.Epidemiology, Biostatistics and Clinical Trials, Istituto Nazionale per la Ricerca sul Cancro—ISTGenoaItaly

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