IG MYC TRANSLOCATIONS OF THE PLASMACYTOMA-PRONE BALB/C STRAIN OCCUR INDEPENDENTLY OF THE GENETIC AND PARENTAL ORIGIN OF THE AFFECTED CHROMOSOME-6, CHROMOSOME-12, AND CHROMOSOME-15/

Virtually all murine plasmacytomas (MPCs) carry chromosomal translocat ions that juxtapose myc on chromosome 15 (chr 15) to one of the three immunoglobulin loci carrying chr 6, 12, or 16. Only some mouse strains are susceptible to MPC induction, however, with BALB/c as the outstan ding example. Most other strains are resistant. Our earlier studies wi th reciprocal BALB/c <----> DBA/2 chimeras suggested that part of this susceptibility is determined at the level of the target cell itself ( DBA/2 is MPC resistant). The probability of the Ig/mcy translocation i s one of the possibly relevant variables. Because MPC resistance is do minant over susceptibility, it is conceivable that the translocations prevail due to some deficiency of the Ig rearrangement or Ig-associate d repair mechanisms in BALB/c cells. This could be determined at the l evel of the chromosomes that participate in the translocation or by ge nes on other chromosomes. Here, we show that the substitution of the B ALB/c-derived chr 12, 6, and 15, which carry IgH, kappa, and myc, resp ectively, with their homologs derived from MPC-resistant mice, did not affect MPC susceptibility. The use of Robertsonian 4.12 and 6.15 chro mosomes in this study has also provided us with the opportunity to ass ess the parental derivation of the chromosomes participating in the tr anslocation. In contrast to the human chronic myeloid leukemia (CML)-a ssociated BCR/ABL fusion transcript, where a strong bias was claimed t hat was attributed to imprinting, we have found that the parental chro mosomes were randomly involved in the translocation. We have also show n that the translocations could be of uniparental or biparental origin . (C) 1996 Wiley-Liss, Inc.