We have continued to employ inflammation-induced peritoneal plasmacytoma development in genetically susceptible BALB/c mice as our principal experimental system to further our understanding of the origin, incidence and genetic control of chromosomal translocations that deregulate the expression of the proto-oncogene c-myc. Alexander L. Kovalchuk discovered a novel remodeling-by-deletion mechanism that alters the fine structure of the c-myc-deregulating product of the balanced chromosomal translocation T(12;15) in BALB/c plasmacytomas. He showed that plasma cell tumors harboring illegitimate genetic recombinations between c-myc and the most distal locus of the immunoglobulin heavy-chain gene cluster, Ca, can be derived from precursor cells containing rearrangements between c-myc and the most proximal locus of the immunoglobulin heavy-chain gene cluster, Cm (Oncogene 15, 2369-2377, 1997). The molecular evolution of the T(12;15) in congenic BALB/c mice that harbor a human IL-6 transgene is the focus of ongoing studies.Sung Sup Park has chosen to utilize gene-targeting technology to mimick the functional consequence of the T(12;15) translocation by inserting the c-myc gene into the immunoglobulin (Ig) heavy-chain gene cluster upstream of C m and C a. In addition, he has decided to develop new, accelerated models of plasmacytomagenesis that are based on the transgenic expression of c-myc under the transcriptional control of the Ig light-chain k and l enhancers, or the intronic and 3? Ig heavy-chain enhancers. Allen E. Coleman employed spectral karyotyping (SKY) to learn more about secondary genetic alterations that may occur in the course of peritoneal plasmacytomagenesis in BALB/c mice. Using the established plasmacytoma, MOPC 315, as a model tumor, he was able to demonstrate for the first time that jumping chromosomal translocations can effect the amplification of translocation breakpoint regions which contain activated oncogenes (Blood 93, 4442-4444, 1999). He is currently extending SKY analysis to primary plasmacytomas and has already identified a promiscuous, non-reciprocal translocation of Chr 5 that occurs in 50% of tumors with primary T(12;15) or T(6;15) chromosomal translocations. This finding led us to conclude that Chr 5E may contain an important, but previously unrecognized plasmacytoma progressor gene. - c-myc, chromosomal translocations, plasmacytoma, spectral karyotyping, - Neither Human Subjects nor Human Tissues
