Location of Myc, Igh, and Igk on Robertsonian fusion chromosomes is inconsequential for Myc translocations and plasmacytoma development in mice, but Rb(6.15)-carrying tumors prefer Igk-Myc inversions over Translocations

The location of the Myc and immunoglobulin (lg) loci on metacentric Robertsonian (Rb) fusion chromosomes may affect the development of mouse plasmacytornas (Pcts) by changing the probability with which chromosomal Myc-lg translocations occur. To test this hypothesis, we induced Pcts in BALB/c (C) mice that carried Rb(4.12) and/or Rb(6.15) chromosomes. The Rb mice developed Pcts (n = 198) with similar onset and incidence to that in the inbred C mice. Karyotyping of 70 Rb-carrying Pcts demonstrated that in these tumors, just as in their counterparts in inbred C mice, the lgh heavy-chain locus was translocated with Myc more often than was the lgk light-chain locus. Pcts harboring lgh or lgk on normal and Rb chromosomes showed no bias toward either in generating Myc translocations. These findings indicated that the location of Myc, lgh, and lgk on normal or Rb chromosomes is inconsequential for Myc translocation and Pct development. In contrast, in Rb(6.15) mice, in which chromosomal inversions competed with chromosomal translocations for lgk-Myc juxtapositions, the former occurred more frequently than the latter in the resulting Pcts. This suggested that spatial proximity of lgk and Myc on the same chromosome facilitates the rearrangement of these loci. Myc translocation-depenclent mouse Pct may provide a good model system for furthering our understanding of the relationship of higher-order genome organization in the interphase nucleus, origin of chromosomal translocations, and development of cancer. Published 2005 Wiley-Liss, Inc.