Chromosomal regions involved in the pathogenesis of osteosarcomas

The comparative genomic hybridization technique (CGH) was used to identify common chromosomal imbalances in osteosarcomas (OS), which frequently displ ay complex karyotypic changes. We analyzed 13 high-grade primary tumors, 5 corresponding cell lines, 2 primary tumors grade 2, and I recurrent tumor f rom a total of 16 patients. Some of the CGH results have been verified by f luorescence in situ hybridization (FISH) studies. Gains of chromosomal mate rial were more frequent than losses. Most common gains were observed at 8q (11 cases), 4q (9 cases), 7q (8 cases), 5p (7 cases), and 1p (8 cases). The smallest regions of overlap have been narrowed down to 8q23 (10 cases), 4q 12-13 (8 cases), 5p13-14 (7 cases), 7q31-32 (7 cases), 8q21 (7 cases), and 4q28-31 (5 cases). These data demonstrate that a number of chromosomal regi ons and even two distinct loci on 4q and 89 are involved in the pathogenesi s of OS, with gain of 4q 12-13 chromosomal material representing a newly id entified locus. Seven of 16 cases displayed, besides gain of 8q23 sequences , gain of MYC copies in CGH and FISH. Previous CCH reports confined gain of 8q material to 8cen-q 13, 8q21.3-8q22, and 8q23-qter, whereas our data sug gest that the loci 8q21 and 8q23-24 are affected in the development of OS. In contrast to recent reports, copy number increases at 89 and 1q21 did not have an unfavorable impact on prognosis in the present series. (C) 2000 Wi ley-Liss, Inc.