title: Selective increase in subtelomeric DNA methylation: an epigenetic biomarker for malignant glioma.
abstract: BACKGROUND
  Subtelomeric regions dynamically change their epigenetic pattern during development and progression of several malignancies and degenerative disorders. However, DNA methylation of human subtelomeres and their correlation to telomere length (TL) remain undetermined in glioma.
  
  
  RESULTS
  Herein, we report on the selective changes in subtelomeric DNA methylation at the end of five chromosomes (Chr.) (7q, 8q. 18p, 21q, and XpYp) and ascertain their correlation with TL in patients with glioma. Subtelomeric methylation level was invariably higher in glioma patients compared to the control group, irrespective of their age and tumor grade. In particular, a significant increase in methylation was observed at the subtelomeric CpG sites of Chr. 8q, 21q, and XpYp in tissues, obtained from the brain tumor of glioma patients. In contrast, no significant change in methylation was observed at the subtelomere of Chr. 7q and 18p. Selective changes in the subtelomeric methylation level, however, did not show any significant correlation to the global TL. This observed phenomenon was validated in vitro by inducing demethylation in a glioblastoma cell line (SF-767) using 5-azacytidine (AZA) treatment. AZA treatment caused significant changes in the subtelomeric methylation pattern but did not alter the TL, which supports our hypothesis.
  
  
  CONCLUSIONS
  DNA methylation level dramatically increased at the subtelomere of Chr.8q, 21q, and XpYp in malignant glioma, which could be used as an early epigenetic diagnostic biomarker of the disease. Alterations in subtelomeric methylation, however, have no effects on the TL.
authors.affiliation: Department of Biological Engineering, Center for Cancer Research, Purdue University, West Lafayette, IN 47906 USA.
authors.forename: Samrat Roy
authors.initials: SR
authors.lastname: Choudhury
authors.affiliation: Department of Biological Engineering, Center for Cancer Research, Purdue University, West Lafayette, IN 47906 USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47906 USA.
authors.forename: Jacob R
authors.initials: JR
authors.lastname: Milton
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008 China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biological Engineering, Center for Cancer Research, Purdue University, West Lafayette, IN 47906 USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Irudayaraj
keywords: Epigenetic biomarker; Glioma; Subtelomeric DNA methylation; Telomere length