| Research Abstract |
To get an insight into the expression of epithelial characters and genetic changes associated with the development of bone and soft tissue tumors (BSTTs), we examined the expression of cytokeratin (CK) mRNA and gene rearrangements in BSTTs with epithelial characters, including synovial sarcoma (SS), epithelioid sarcoma (ES) and rhabdoid tumor (RBT). The results obtained during the term of project are as follows.
1. Expression of CK8, CK10, CK14, CK18, or CK19 mRNA was detected with RNA-PCR in SS,ES,RBT,and control BSTTs without epithelial characters, suggesting a wide spectrum of CK gene expression in mesenchymal malignancies so far believed to be non-epithelial in origin.
2. A chromosomal translocation, t (X ; 18) (p11 ; q11), was found to be specifically associated with SS,although no such specific chromosome changes were observed in ES and RBT.The fluorescence in situ hybridization using the YAC and cosmid clones obtained from the breakpoint regions of t (X ; 18) showed that the rearranged X chromosome has the breakpoint in two separate regions within the clusters of ornithine aminotransferase pseudogenes (OATL1 and OATL2) on the short arm at p11.2.
3. The t (X ; 18) was found, by a collaborating British research group, to juxtapose the SSX gene located on Xp11.2 to the SYT gene located on 18q11.2, by which a fusion transcript is generated. We showed that the SSX/SYT chimeric gene mRNA expression is specifically associated with SS cases with t (X ; 18) and not found in other BSTTs without this translocation, providing a useful means for the diagnosis of SS.
4. CA-repeat primed PCR (CAP-PCR), which was developed by us for monitoring the genomic polymorphism of animal genomes, detected the genomic instability in a variety of BSTTs, suggesting a wide spectrum of genetic changes in the development of BSTTs.
|
