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Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, α-PIX and sorcin

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Abstract

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), α-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.

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Acknowledgements

This work was supported by special grants for Strategic Advanced Research on “Cancer” from the Ministry of Education, Science, Sports and Culture of Japan; by a Research Grant from the Ministry of Health and Welfare of Japan; and by a Research for the Future Program Grant of The Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Molecular Biology, Institute of Gerontology. Nippon Medical School, 1-396, Kosugi-cho, Nakahara-ku, 211-8533, Kawasaki, Japan

    Takashi Yokota, Jun Kouno & Masamitsu Onda

  2. Department of Neurosurgery, Nippon Medical School, 1-1-5, Sendagi, Bunnkyo-ku, 113-8603, Tokyo, Japan

    Jun Kouno, Koji Adachi, Hiroshi Takahashi & Akira Teramoto

  3. Department of Pathology, Nippon Medical School Second Hospital, Nippon Medical School, 1-396, Kosugi-cho, 211-8533, Kawasaki, Japan

    Koshi Matsumoto

  4. Division of Surgical Pathology, Nippon Medical School Hospital, Tokyo, Japan

    Yuichi Sugisaki

  5. SNP Research Center, Institute of Physical and Chemical Research, Suehiro-cho, 230-0045, Yokohama, Japan

    Tatsuhiko Tsunoda

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  1. Takashi Yokota
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Correspondence to Takashi Yokota.

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Yokota, T., Kouno, J., Adachi, K. et al. Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, α-PIX and sorcin. Acta Neuropathol 111, 29–38 (2006). https://doi.org/10.1007/s00401-005-1085-6

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  • DOI: https://doi.org/10.1007/s00401-005-1085-6

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