Epigenetic inactivation of the hMLH1 gene in progression of gliomas

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14 Citations (Scopus)

Abstract

Gliomas (GLs) are characterized by highly variable biologic behavior. After surgical resection and postoperative therapy, they frequently recur with the same or higher-grade histology. Although a number of genetic aberrations have been described in different histologic types of GLs, the molecular mechanisms of histologic and clinical progression are poorly understood. In this study, we have performed longitudinal mismatch repair gene polymerase chain reaction-single strand conformation polymorphism and methylation analysis in paired samples of primary and recurrent GLs to reveal whether the inactivation of the normal DNA repair mechanism is associated with tumor progression. Polymerase chain reaction-single strand conformation polymorphism analysis of the hMLH1 gene was performed in 24 cases, in each case the samples of the first and second biopsies being evaluated simultaneously, but no alterations in the hMLH1 gene were found. Methylation analysis of the CpG sites in the hMLH1 promoter revealed a total of 4 (16.6%) hypermethylations in recurrent GLs. These results suggest that hMLH1 promoter hypermethylation may occur in low-grade GLs, associated with the development and progression of moderate malignant GL, but not with structural alterations in the hMLH1 gene. It seems that hMLH1 promoter hypermethylation is an early event in the development and progression or the clonal evolution of GLs, this gene inactivation proving stable even on tumor recurrence.

Original languageEnglish
Pages (from-to)104-107
Number of pages4
JournalDiagnostic Molecular Pathology
Volume16
Issue number2
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Glioma
  • Hypermethylation
  • Tumor progression
  • hMLH1 gene

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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