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© 1994 Oxford University Press

OTHER

Molecular cloning of the synovial sarcoma-specific translocation (X;18)(p11.2;q11.2) breakpoint

B. de Leeuw*, M. Balemans, D.Olde Weghuis, R. Seruca1, M. Janz2, M.T. Geraghty3, S. Gilgenkrantz4, H.H. Ropers and A.Geurts van Kessel

Department of Human Genetics, University Hospital PO Box 9101, 6500 HB Nijmegen, The Netherlands 1Department of Pathology, IPATIMUP, Medical Faculty of Porto Porto, Portugal 2Institute for Molecular Biology, Medical School Hannover, Germany 3Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine Baltimore, MD, USA 4Laboratoire de Genetique, Centre Regional de Transfusion Saguine Nancy, France

*To whom correspondence should be addressed

Received January 31, 1994; Accepted March 14, 1994

The chromosomal translocation (X;18)(p11.2;q11.2) represents the cytogenetic hallmark of human synovlal sarcomas. Two related but distinct breakpoints within band Xp11.2 were reported previously by us and others using breakpoint-spanning YACs in conjunction with FISH. Interestingly, we found that the occurrence of these alternative breakpoints corresponds to the presence of different histologic characteristics of the tumors Involved. Here we report the isolation, via subcloning of one of our YAC-derived cosmlds, of probes which specifically hybridize to altered restriction fragments in tumor DNAs as compared to normal controls. By using a synovial sarcoma-derived der(X) containing somatic cell hybrid, which exhibits the more distal breakpoint, one of these aberrantly hybridizing fragments could be isolated via preparative gel electrophoresis. This fragment appears to contain chromosome X- and 18-derlved 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 contains the translocation breakpoint region. In addition, our results indicate that, in contrast to our findings on the X chromosome, a single locus on chromosome 18 may be Involved in the development of different (sub)types of synovlal sarcoma.


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