Faculty Collaboration Database

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. Genes Chromosomes Cancer 2005 Apr;42(4):416-26

Date

01/13/2005

Pubmed ID

15645495

DOI

10.1002/gcc.20149

Scopus ID

2-s2.0-13944249559 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

The location of the Myc and immunoglobulin (Ig) loci on metacentric Robertsonian (Rb) fusion chromosomes may affect the development of mouse plasmacytomas (Pcts) by changing the probability with which chromosomal Myc-Ig 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 Igh heavy-chain locus was translocated with Myc more often than was the Igk light-chain locus. Pcts harboring Igh or Igk on normal and Rb chromosomes showed no bias toward either in generating Myc translocations. These findings indicated that the location of Myc, Igh, and Igk 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 Igk-Myc juxtapositions, the former occurred more frequently than the latter in the resulting Pcts. This suggested that spatial proximity of Igk and Myc on the same chromosome facilitates the rearrangement of these loci. Myc translocation-dependent 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.

Author List

Silva S, Wiener F, Klein G, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chromosome Inversion
Humans
Immunoglobulin Heavy Chains
Immunoglobulins
Mice
Mice, Inbred BALB C
Plasmacytoma
Proto-Oncogene Proteins c-myc
Recombination, Genetic
Translocation, Genetic