Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma.
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 was 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.
Hisaoka
Masanori
M
Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Tanaka
Atsuko
A
Hashimoto
Hiroshi
H
D001483:Base Sequence; D017931:DNA Primers; D029721:Drosophila Proteins; D005091:Exons / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007438:Introns / Q000235:genetics; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015183:Restriction Mapping; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D029721:Drosophila Proteins; D011494:Protein Kinases; C092745:LATS1 protein, human; C093503:wts protein, Drosophila; D017346:Protein Serine-Threonine Kinases