Abstract Tenosynovial giant cell tumor (TGCT) is the most common benign tumor of synovium and tendon sheath. Cytogenetic data indicate that 1p11–13 is the re- gion most frequently involved in structural rearrange- ments. With the aim of eventually identifying the genes associated with TGCT development, we have investigat- ed 1p11–13 breakpoints using fluorescence in situ hybrid- ization (FISH) analysis, with a panel of yeast artificial chromosome (YAC) probes covering 1p11–21. Twenty- six tumors were analyzed by G-banding, and 24 of these showed a breakpoint in 1p11–13. The cytogenetic find- ings add to previous observations that, among a variety of translocations involving 1p11–13, chromosome 2 is the most common translocation partner, with a breakpoint in 2q35–37. This aberration was found in eight cases. Other recurrent translocation partners, found in two or three cases, were 5q22–31, 11q11–12, and 8q21–22. Material from 21 tumors was available for FISH analysis, which revealed that the breakpoints clustered to one region spanned by two YAC probes, 914F6 and 885F12 located in 1p13.2, in 18 cases. Bacterial artificial chromosome probes were used to map the recurrent breakpoint on chromosome 2. In four of seven cases there was a break- point within the sequence covered by probe 260J21, where the RDC1 gene is located, a gene reported to fuse with HMGIC in lipomas with a 2;12 translocation. Keywords Tenosynovial giant cell tumor · Cytogenetics · FISH · Breakpoint mapping Introduction Tenosynovial giant cell tumors (TGCTs) involve the fibrous sheaths of tendons. They are benign lesions, with some capacity for local recurrence, but rare malignant forms have been described [1]. TGCTs occur as a local- ized form, predominantly involving the fingers, and a less-common, diffuse form affecting various sites, pri- marily the knee, ankle, and foot [3, 23]. These tumors may occur at any age but affect mainly middle-aged per- sons, and the sex ratio for localized tumors in particular is skewed toward women [3]. To date, 30 cases of TGCT with clonal chromosome aberrations have been reported [15]. All cases have had near- or pseudodiploid karyotypes, mostly with simple structural and/or numerical aberrations. The most com- mon numerical changes are gain of chromosomes 5 and 7, which in some cases occur as the sole anomalies. Among the structural aberrations, the short arm of chro- mosome 1 is frequently involved, with a clustering of breakpoints in the chromosome segment 1p11–13. Although 1p11–13 has been found to recombine with several other chromosome segments, a recurrent t(1;2) (p11;q35–36) has been identified [2]. Among published cases, there are no karyotypic differences between local- ized and diffuse tumors, except for trisomies 5 and/or 7 being more common in the diffuse form [22]. It has been debated whether TGCT is a neoplastic lesion or a reac- tive, proliferative process [3]. Although the observation of polyclonal X-chromosome inactivation in pigmented villonodular synovitis [19] might seem to favor the latter view, the frequent findings of non-random, clonal chro- mosome aberrations can be taken as strong support for a neoplastic origin [4, 17, 22]. In the present study, we have analyzed TGCTs cyto- genetically using chromosome banding. These tumors and those previously analyzed in our laboratories were M. Nilsson ( ✉ ) · M. Höglund · I. Panagopoulos · F. Mertens N. Mandahl Department of Clinical Genetics, University Hospital, 221 85 Lund, Sweden e-mail: malin.nilsson@klingen.lu.se Tel.: +46-46-173398, Fax: +46-46-131061 R. Sciot Department of Pathology, University of Leuven, Leuven, Belgium P. Dal Cin Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA M. Debiec-Rychter Center for Human Genetics, University of Leuven, Leuven, Belgium Virchows Arch (2002) 441:475–480 DOI 10.1007/s00428-002-0640-y ORIGINAL ARTICLE M. Nilsson · M. Höglund · I. Panagopoulos R. Sciot · P. Dal Cin · M. Debiec-Rychter · F. Mertens N. Mandahl Molecular cytogenetic mapping of recurrent chromosomal breakpoints in tenosynovial giant cell tumors Received: 14 December 2001 / Accepted: 12 February 2002 / Published online: 13 April 2002 © Springer-Verlag 2002