CHROMOSOMAL INSTABILITY IN FIBROBLASTS AND MESENCHYMAL TUMORS FROM 2 SIBS WITH ROTHMUND-THOMSON-SYNDROME

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genoderm atosis associated with increased risk of mesenchymal tumors. The putat ive gene has been provisionally assigned to chromosome 8. Using a cyto genetic-molecular approach, we studied lymphocytes, fibroblasts, osteo sarcoma (OS) and malignant fibrous histiocytoma (MFH) from 2 affected fraternal twins, looking for constitutive markers of chromosome instab ility and tumor chromosomal changes which might reflect the common gen etic background. The rate of spontaneous chromosome aberrations was no t increased in lymphocytes. Conversely, karyotyping of primary fibrobl asts from one sib evidenced chromosome breaks and both numerical and s tructural chromosome changes in 24% and 17% of the metaphases respecti vely. FISH of a 8q21.3 cosmid allowed us to detect trisomy of the targ et region on 7% of fibroblast nuclei from both sibs, 47% and 12% of OS and MFH cells. Pronounced chromosomal instability and clonal rearrang ements leading to different chromosome-8 derivatives were detected in both tumors. CGH experiments showed multiple gains/losses, among which del(6q), also revealed by cytogenetics, and 7p gain were common, wher eas 8q amplification was present only in OS. Chromosomal instability, observed in fibroblasts from the RTS patients studied, accounts for th e increased risk of mesenchymal tumors in these patients. Int. J. Canc er 77:504-510, 1998. (C) 1998 Wiley-Liss, Inc.