Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene

Masayuki Kanamori, Hiroyuki Kon, Takahiro Nobukuni, Sachio Nomura, Kokichi Sugano, Shoji Mashiyama, Toshihiro Kumabe, Takashi Yoshimoto, Mark Meuth, Takao Sekiya, Yoshinori Murakami

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

High-frequent microsatellite instability (MSI-H) was detected in two of the 80 gliomas examined, whlie the other 78 gliomas showed microsatellite stable (MSS) phenotype, Both of the two MSI-H tumors were glioblastomas which developed in teenage patients. One of the patient was diagnosed as having Turcot's syndrome and had a germline mutation in the hMLH1 gene. Loss of expression due to promoter methylation was selectively observed in the wild type allele of the hMLH1 gene in the tumor of this patient. The other patient had neither a family history nor a past personal history of malignancy. Although no mutation in the mismatch repair genes was detected in the tumor of this patient, the level of expression of the hMLH1 gene was markedly decreased and the promoter sequence of the gene was highly methylated. In the tumor of this patient, the PTEN1 gene, one of the genes carrying microsatellite sequences in their coding regions, was altered by a slippage mutation within five adenine repeat sequences. These findings indicate that the genetic or epigenentic inactivation of the hMLH1 gene is involved in a subset of early-onset gliomas and the PTEN1 gene could be a downstream target for mutation as observed in glioblastoma without MSI.

Original languageEnglish
Pages (from-to)1564-1571
Number of pages8
JournalOncogene
Volume19
Issue number12
DOIs
Publication statusPublished - 2000 Mar 16

Keywords

  • Glioma
  • Microsatellite instability
  • Promoter methylation
  • The PTEN1 gene
  • The hMLH1 gene
  • Turcot's syndrome

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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