Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma
Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma
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DOI：
10.1097/01.lab.0000032381.68634.ca
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发表时间：
2002-10-01
影响因子：
5
通讯作者：
Hashimoto, H
中科院分区：
文献类型：
--
作者：
Hisaoka, M;Tanaka, A;Hashimoto, H
h-warts/LATS 1是果蝇疣肿瘤抑制基因的人类同源物，其作为有丝分裂装置的组成部分发挥作用。据报道，LATS 1缺陷型（Lats 1（-/-））小鼠可发生卵巢间质肿瘤和软组织肉瘤。我们研究了50例人类软组织肉瘤中h-warts/LATS 1的状态，以解决其作为人类肉瘤发展中肿瘤抑制因子的潜在功能。在我们的RT-PCR检测中，50例肉瘤中有7例（14%）（4例粘液样脂肪肉瘤中的3例，7例平滑肌肉瘤中的3例，9例恶性纤维组织细胞瘤中的1例）没有h-warts/LATS 1表达或表达减少，表明基因表达下调。我们进一步分析了这七个肉瘤中h-warts/LATS 1的改变。使用染色体6 q23 -25.1的微卫星标记，其中h-warts/LATS 1是本地化的，该位点的等位基因的丢失被检测到在一个平滑肌肉瘤，其中错义点突变的h-warts/LATS 1 v的PCR单链构象多态性检测。在其他6例肉瘤中，5'端启动子区域的CpG二核苷酸簇被高甲基化。我们的数据表明，h-warts/LATS 1的分子改变可能是人类肉瘤发生的病理重要性。
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.