PREVIOUSLY HIDDEN CHROMOSOME-ABERRATIONS IN T(12-15)-POSITIVE BALB C PLASMACYTOMAS UNCOVERED BY MULTICOLOR SPECTRAL KARYOTYPING/

The majority of BALB/c mouse plasmacytomas harbor a balanced T(12;15) chromosomal translocation deregulating the expression of the proto-onc ogene c-myc. Recent evidence suggests that the T(12;15) is an initiati ng tumorigenic mutation that occurs in early plasmacytoma precursor ce lls. However, the possible contribution of additional chromosomal aber rations to the progression of plasmacytoma development has been largel y ignored, Here we use multicolor spectral karyotyping (SKY) to evalua te 10 established BALB/c plasmacytomas in which the T(12;15) had been previously detected by G banding, SKY readily confirmed the presence o f this translocation in all of these tumors and in three plasmacytomas newly identified secondary cytogenetic changes of the c-myc-deregulat ing chromosome (Chr) T(12;15). In addition, numerous previously unknow n aberrations were found to be scattered throughout the genome, which was interpreted to reflect the general genomic instability of plasmacy tomas, instability of this sort was not uniform, however, because only half of the tumors were heavily rearranged, Seven apparent hot spots of chromosomal rearrangements (40% incidence) were identified and mapp ed to Chrs 1B, 1G-H, 2G-H1, 4C7-D2, 12D, 14C-D2, and XE-F1. Two of the se regions, Chr 1B and Chr 4C7-D2, are suspected to harbor plasmacytom a susceptibility loci; Pctr(1) and Pctr(2) on Chr 4C7-D2 and as yet un named loci on Chr 1B, These results suggest that secondary chromosomal rearrangements contribute to plasmacytoma progression in BALB/c mice. To evaluate the biological significance of these rearrangements, SKY will be used in follow-up experiments to search for the presence of re current and/or consistent secondary cytogenetic aberrations in primary BALB/c plasmacytomas.