Structural and functional evidence for the presence of tumor suppressor genes on the short arm of chromosome 10 in human gliomas

Hiroyuki Kon, Yukihiko Sonoda, Toshihiro Kumabe, Takashi Yoshimoto, Takao Sekiya, Yoshinori Murakami

    Research output: Contribution to journalArticle

    55 Citations (Scopus)

    Abstract

    Loss of heterozygosity (LOH) observed at polymorphic loci on both arms of chromosome 10 in many human gliomas suggests the presence of multiple tumor suppressor genes on this chromosome. Recently, the PTEN/MMAC1 gene on 10q23 was isolated as one of these putative glioma suppressors. To determine the subchromosomal localization of others, we analysed 79 gliomas for LOH using 30 polymorphic microsatellite markers on the short arm and 10 markers on the long arm of chromosome 10. Twenty tumors showed LOH at all the loci examined, while 17 others showed LOH at loci on a portion of chromosome 10. Deletion mapping of the latters demonstrated that two distinct regions, encompassing genetic distances of 5.6 cM on 10p15 and 5.5 cM on 10p14, were lost frequently. Introduction of chromosomal fragments 10p14-p15, which included the entire region on 10p15 and a portion of that on 10p14 assigned by deletion mapping, into the human glioblastoma cell line T98G through microcell-mediated chromosome transfer markedly suppressed colony forming ability in soft agar compared with parental T98G cells. The combined results of structural and functional analyses strongly suggest that aberrations of the tumor suppressor gene(s) within chromosomal region 10p14-p15 are involved in development of human gliomas.

    Original languageEnglish
    Pages (from-to)257-263
    Number of pages7
    JournalOncogene
    Volume16
    Issue number2
    DOIs
    Publication statusPublished - 1998 Jan 15

    Keywords

    • Chromosome 10p
    • Chromosome transfer
    • Glioma
    • Loss of heterozygosity
    • Tumor suppressor gene

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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