학술논문
Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: association with tumor WHO grade and clinical outcome
Document Type
Original Paper
Author
Di Vinci, Angela; 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
Source
Journal of Cancer Research and Clinical Oncology. January 2012 138(1):35-47
Subject
Language
English
ISSN
0171-5216
1432-1335
1432-1335
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.