Molecular characteristics of pediatric non-ependymal, non-pilocytic gliomas associated with resistance to temozolomide

Taketo Ezaki, Hikaru Sasaki, Yuichi Hirose, Tomoru Miwa, Kazunari Yoshida, Takeshi Kawase

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Abstract

Temozolomide constitutes current standard of care for adult patients with high-grade gliomas. However, results for pediatric gliomas are rather disappointing. In order to investigate the molecular differences between pediatric and adult gliomas that could affect sensitivity to temozolomide, we studied 23 pediatric non-ependymal, non-pilocytic gliomas in comparison to 59 consecutive adult gliomas for the expression of O 6-methylguanine methyltransferase (MGMT) and the DNA mismatch repair protein, mutS homolog 6 (MSH6) by immunohistochemistry, as well as for the presence or absence of promoter methylation of the MGMT gene by methylation-specific PCR. The expression of MGMT in pediatric gliomas was significantly higher than in adult gliomas, as shown by immunohistochemistry (p=0.00004). This association was conserved if statistical analysis was carried out only in astrocytic tumors (diffuse astrocytoma, anaplastic astrocytoma and glioblastoma, p=0.00007), or in oligodendroglial tumors (oligodendroglioma and anaplastic oligodendroglioma, p=0.020). Although methylation-specific PCR was successfully performed only in 15 pediatric gliomas, it also showed a trend toward less frequent methylation in pediatric as opposed to adult gliomas (p=0.242). MSH6 was almost equally expressed in pediatric and adult gliomas. Pediatric gliomas appear to have a distinct molecular profile associated with resistance to temozolomide. Higher expression of MGMT and a trend toward less frequent methylation of the promoter region of MGMT gene may partly account for relative resistance to temozolomide in pediatric gliomas as compared to adult gliomas.

Original languageEnglish
Pages (from-to)1101-1105
Number of pages5
JournalMolecular Medicine Reports
Volume4
Issue number6
DOIs
Publication statusPublished - 01-11-2011

Fingerprint

temozolomide
Pediatrics
Glioma
Methylation
Methyltransferases
MutS DNA Mismatch-Binding Protein
Oligodendroglioma
Tumors
Genes
Astrocytoma
O(6)-Methylguanine-DNA Methyltransferase
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cancer Research
  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Oncology

Cite this

Ezaki, Taketo ; Sasaki, Hikaru ; Hirose, Yuichi ; Miwa, Tomoru ; Yoshida, Kazunari ; Kawase, Takeshi. / Molecular characteristics of pediatric non-ependymal, non-pilocytic gliomas associated with resistance to temozolomide. In: Molecular Medicine Reports. 2011 ; Vol. 4, No. 6. pp. 1101-1105.
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Molecular characteristics of pediatric non-ependymal, non-pilocytic gliomas associated with resistance to temozolomide. / Ezaki, Taketo; Sasaki, Hikaru; Hirose, Yuichi; Miwa, Tomoru; Yoshida, Kazunari; Kawase, Takeshi.

In: Molecular Medicine Reports, Vol. 4, No. 6, 01.11.2011, p. 1101-1105.

Research output: Contribution to journalArticle

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