MOLECULAR-CLONING OF THE SYNOVIAL SARCOMA-SPECIFIC TRANSLOCATION (X18)(P11.2Q11.2) BREAKPOINT

The chromosomal translocation (X;18)(p11.2;q11.2) represents the cytog enetic hallmark of human synovial sarcomas. Two related but distinct b reakpoints within band Xp11.2 were reported previously by us and other s using breakpoint-spanning YACs in conjunction with FISH. Interesting ly, we found that the occurrence of these alternative breakpoints corr esponds to the presence of different histologic characteristics of the tumors involved. Here we report the isolation, via subcloning of one of our YAC-derived cosmids, of probes which specifically hybridize to altered restriction fragments in tumor DNAs as compared to normal cont rols. By using a synovial sarcoma-derived der(X) containing somatic ce ll hybrid, which exhibits the more distal breakpoint, one of these abe rrantly hybridizing fragments could be isolated via preparative gel el ectrophoresis. This fragment appears to contain chromosome X- and 18-d erived sequences, as revealed by both FISH on normal metaphase spreads and Southern blot analysis of X- and 18-only somatic cell hybrids. We conclude that this genomic fragment is chimaeric in nature and contai ns the translocation breakpoint region. In addition, our results indic ate that, in contrast to our findings on the X chromosome, a single lo cus on chromosome 18 may be involved in the development of different ( sub)types of synovial sarcoma.