Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma

被引:77
作者
Hisaoka, M [1 ]
Tanaka, A [1 ]
Hashimoto, H [1 ]
机构
[1] Univ Occupat & Environm Hlth, Dept Pathol & Oncol, Sch Med, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan
基金
日本学术振兴会;
关键词
D O I
10.1097/01.LAB.0000032381.68634.CA
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
h-warts/LATS1 is a human homolog of the Drosophila warts tumor suppressor gene, which functions as a component of the mitotic apparatus. LATS1-deficient (Lats1(-/-)) mice have been reported to develop ovarian stromal tumors and soft tissue sarcomas. We investigated the status of the h-warts/LATS1 in 50 human soft tissue sarcomas to address its potential function as a tumor suppressor in human sarcoma development. In our RT-PCR assay, 7 (14%) (3 of 4 myxoid liposarcomas, 3 of 7 leiomyosarcomas, 1 of 9 malignant fibrous histiocytomas) of 50 sarcomas examined had no or a reduced expression of the h-warts/LATS1, indicating down-regulated gene expression. We further analyzed alterations of the h-warts/LATS1 in these seven sarcomas. Using microsatellite markers for chromosome 6q23-25.1, to which the h-warts/LATS1 is localized, an allelic loss of this locus was detected in one leiomyosarcoma, in which a missense point mutation of the h-warts/LATS1 v as detected by PCR single-strand conformation polymorphism. Clusters of CpG dinucleotides in a 5' putative promoter region were hypermethylated in the other six sarcomas. Our data suggest that the molecular alterations of the h-warts/LATS1 could be of pathologic importance in human sarcomagenesis.
引用
收藏
页码:1427 / 1435
页数:9
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