Translocation remodeling in the primary BALB/c plasmacytoma TEPC 3610

Myc-activating chromosomal 12:15 translocations, the hallmark mutations of inflammation-induced BALB/c plasmacytomas, have recently been shown to unde rgo remodeling by isotype switch-like generic recombinations that remove si milar to 180 kb of immunoglobulin heavy-chain sequence in the vicinity of t he rearranged, expressed Myc gene. Here we combine cytogenetic data on the 12;15 translocation (SKY and FISH) with the molecular analysis of key junct ion sites (long-range PCR followed by DNA sequencing) to demonstrate that t ranslocation remodeling occurred as an infrequent, stepwise, and disomic tu mor progression event in the tetraploid, fully transformed, and transplanta ble plasmacytoma TEPC 3610. This result was used. in conjunction with previ ously obtained molecular data on five other primary plasmacytomas, to devis e a hypothesis that predicts that the selective pressure to undergo translo cation remodeling may be predetermined by the location of the break site in Myc. The pressure may be low if the break occurs 5' of the normal promoter region of Myc, but it may be considerably stronger if the break occurs 3' of the Myc promoter. Published 2001 Wiley-Liss, Inc(dagger).