SUBLOCALIZATION OF THE SYNOVIAL SARCOMA-ASSOCIATED T(X-18) CHROMOSOMAL BREAKPOINT IN XP11.2 USING COSMID CLONING AND FLUORESCENCE INSITU HYBRIDIZATION

In a previous study we localized the synovial sarcoma-associated t(X;1 8)(p11;q11) breakpoint within the ornithine aminotransferase-like 1 (O ATL1) cluster on the X chromosome. This localization was delineated fr om both somatic cell hybrid and fluorescence in situ hybridization (FI SH) analysis of patient material, using OAT-specific cDNA and YAC prob es. Simultaneously, Knight et al. (1992, MoL Hum. Genet, in press) map ped this same breakpoint in their patient material adjacent to the mor e proximal OATL2 region on the X chromosome. Here we report the analys is of two additional tumors and demonstrate that again in these cases the chromosomal break occurs within the OATL1 cluster. In order to fur ther specify the breakpoint, we subcloned the OATL1 YAC (no. 2) into c osmids. At least one of these cosmids (0.38) hybridizes to sequences t hat bracket the translocation breakpoint, as demonstrated by both Sout hern blot and FISH analysis. These observations confirm and substantia te our previous findings. In addition, cosmid 0.38 should be a valuabl e instrument for the ultimate isolation and identification of the gene (s) involved in the development of synovial sarcoma.