2002 Fiscal Year Final Research Report Summary
Molecular Analyses of h-Warts/Latsl Alterations in Human neoplasms
| Project/Area Number |
12670184
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
HASHIMOTO Hiroshi University of Occupational and Environmental Health, School of Medicine, Professor, 医学部, 教授 (10128069)
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| Co-Investigator(Kenkyū-buntansha) |
HISAOKA Masanori University of Occupational and Environmental Health, School of Medicine, Associate professor, 医学部, 助教授 (40218706)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Soft tissue tumor / Tumor suppressor gene / Lats1 / Gene analysis / Molecular cytogenetics / Gene promoter / Methylated CpG |
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| Research Abstract |
h-Warts/LATS1 is a human homologue of the Drosophila warts tumor suppressor gene, that functions as a component of the mitotic apparatus, and 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 reverse transcription-polymerase chain reaction (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 7 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 misssense point mutation of the h-Warts/LATS1 was detected by PCR-single-strand conformation polymorphism. Clusters of CpG dinucleotides in a 5' putative promoter region were hypermethylated in the other 6 sarcomas. Our data suggest that the molecular alterations of the h-Warts/LATS1 could be of pathological importance in human sarcomagenesis, and provide potential clues for further clinical treatments of human soft tissue sarcomas.
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