Brain Tumor Res Treat.  2014 Apr;2(1):29-35. 10.14791/btrt.2014.2.1.29.

Aberrant CpG Islands Hypermethylation Profiles in Malignant Gliomas

• Kim KR
• Kim E
• Son EI

• KMID: 1734665
• DOI: http://doi.org/10.14791/btrt.2014.2.1.29

Abstract

BACKGROUND
The authors analyzed whether the promoter hypermethylation of cancer-related genes was involved in the tumorigenesis of malignant gliomas.
METHODS
A total of 29 patients received surgery and histologically confirmed to have malignant gliomas from January 2000 to December 2006. The promoter methylation status of several genes, which were reported to be frequently methylated in malignant gliomas, was investigated using methylation-specific polymerase chain reaction.
RESULTS
All cases of malignant gliomas represented the promoter hypermethylation in at least 2 or more genes tested. Of 29 tumors, 28 (96.55%) showed concurrent hypermethylation of 3 or more genes. Ras association domain family member 1, epithelial cadherin, O-6 methyl guanine DNA methyltransferase, thrombospondin 1, p14 and adenomatous polyposis coli were frequently methylated in high grade gliomas including glioblastomas, anaplastic astrocytomas, and anaplastic oligodendrogliomas.
CONCLUSION
Aberrant hypermethylation profile was closely related with malignant gliomas suggesting that epigenetic change may play a role in the development of malignant gliomas. Two or three target genes may provide useful clues to the development of the useful prognostic as well as diagnostic assays for malignant gliomas.

Keyword

Brain neoplasms; CpG island; Epigenomics; Methylation

MeSH Terms

Adenomatous Polyposis Coli
Astrocytoma
Brain Neoplasms
Carcinogenesis
CpG Islands*
DNA
Epigenomics
Glioblastoma
Glioma*
Guanine
Humans
Methylation
Oligodendroglioma
Polymerase Chain Reaction
Thrombospondin 1
DNA
Guanine
Thrombospondin 1

Figure

• 

  Fig. 1 Representative data of methylation-specific PCR analysis of DNA samples for peripheral bloods and malignant brain tumors. L, size marker (100-bp DNA ladder); P, positive control (a normal lymphocyte DNA treated with Sss1 methylase before bisulfite modification); N, negative control (distilled water without template DNA). T: tumor, B: blood, M: methylated, U: unmethylated, E-cadherin: epithelial cadherin, MGMT: O-6 methyl guanine DNA methyltransferase, RASSF1A: Ras association domain family member 1, THBS1: thrombospondin 1, APC: adenomatous polyposis coli, COX-2: cyclooxygenase 2, TIMP3: tissue inhibitor metalloproteinase 3, GSTP1: glutathione S-transferase pi 1, hMLH1: human mutL homologue 1, DNA: deoxyribonucleic acid.

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