TY - JOUR
T1 - Structural and functional evidence for the presence of tumor suppressor genes on the short arm of chromosome 10 in human gliomas
AU - Kon, Hiroyuki
AU - Sonoda, Yukihiko
AU - Kumabe, Toshihiro
AU - Yoshimoto, Takashi
AU - Sekiya, Takao
AU - Murakami, Yoshinori
N1 - Funding Information:
We thank Drs Hans Albertsen, Steven C Gerken and Raymond L White for providing information about the polymorphic markers, Dr Conover Talbot, Jr for providing information about chromosomal localization of the markers and Dr Ruth Foltz for expert assistance in editing the manuscript. This work was supported in part by a Grant-in Aid from the Ministry of Health and Welfare of Japan for the 2nd Comprehensive 10-Year Strategy for Cancer Control, and by a Grant for Research of Aging and Health from the Ministry of Health and Welfare of Japan.
PY - 1998/1/15
Y1 - 1998/1/15
N2 - 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.
AB - 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.
KW - Chromosome 10p
KW - Chromosome transfer
KW - Glioma
KW - Loss of heterozygosity
KW - Tumor suppressor gene
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U2 - 10.1038/sj.onc.1201488
DO - 10.1038/sj.onc.1201488
M3 - Article
C2 - 9464544
AN - SCOPUS:0032518924
VL - 16
SP - 257
EP - 263
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 2
ER -