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

Oncogene volume 19, pages 1564–1571 (2000)Cite this article

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.

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Acknowledgements

We thank Dr Raymond L White for valuable comments and suggestions. This work was supported in part by a Grant-in Aid for the Second Comprehensive 10-Year Strategy for Cancer Control, and a Grant for Research on Human Genome and Gene Therapy, from the Ministry of Health and Welfare, Japan; by a Grant-in-Aid for Special Projects for Cancer Research from the Ministry of Education, Science, Sports and Culture of Japan. T Nobukuni is a recipient of Research Resident Fellowships from the Foundation for Promotion of Cancer Research of Japan.

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Authors and Affiliations

  1. Oncogene Division, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

    Masayuki Kanamori, Hiroyuki Kon, Takahiro Nobukuni, Takao Sekiya & Yoshinori Murakami

  2. Division of Neurosurgery, Tohoku University School of Medicine, Sendai, 980-8575, Japan

    Masayuki Kanamori, Hiroyuki Kon, Toshihiro Kumabe & Takashi Yoshimoto

  3. Clinical Laboratory, National Cancer Center Hospital, Tokyo, 104-0045, Japan

    Sachio Nomura & Kokichi Sugano

  4. Iwaki Kyoritu Hospital, Iwaki, Japan

    Shoji Mashiyama

  5. Institute for Cancer Studies, University of Sheffield, Sheffield, S10 2RX, UK

    Mark Meuth

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  1. Masayuki Kanamori
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Kanamori, M., Kon, H., Nobukuni, T. et al. Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene. Oncogene 19, 1564–1571 (2000). https://doi.org/10.1038/sj.onc.1203454

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