Faculty Collaboration Database

E mu/S mu transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells. Oncogene 2003 May 08;22(18):2842-50

Date

05/14/2003

Pubmed ID

12743607

DOI

10.1038/sj.onc.1206345

Scopus ID

2-s2.0-0037616590 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Misguided immunoglobulin (Ig) class switch recombination (CSR) has been implicated in the origin of Myc-activating chromosomal translocations, T(12;15), in BALB/c mouse plasmacytomas (PCTs). CSR has also been involved in the progression of T(12;15); for example, the approximation of Myc to the 3'-C alpha enhancer. This study provides evidence for an additional mechanism by which aberrant CSR may facilitate T(12;15): transposition of Ig heavy-chain (IgH) sequences to Myc. Five IgH transposons containing the intronic heavy-chain enhancer, E mu, and a truncated switch mu region, S mu, were found in the first intron of Myc in lymph node cells of IL-6 transgenic BALB/c mice. In two cases E mu/S mu transposition primed Myc to get involved in apparent trans-chromosomal CSR to C gamma 1, presumably leading to T(12;15). Translocations preceded by E mu/S mu transposition can sometimes be distinguished from de novo translocations by molecular fingerprints in translocation breakpoint regions (Ig switch region [S] inversions and unusual gene orders in composite S regions). The presence of such fingerprints in some PCTs suggests that the tumors sometimes evolve from transposition-bearing precursors. We propose that E mu/S mu transposition to Myc may facilitate plasmacytomagenesis by sensitizing Myc to undergo T(12;15) translocation. T(12;15), in turn, juxtaposes Myc to the 3'-C alpha enhancer, which appears to be required for deregulating Myc in a manner that is conducive to PCT development.

Author List

Kovalchuk AL, Kim JS, 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
B-Lymphocytes
Base Sequence
Chromosome Mapping
DNA Primers
DNA Transposable Elements
Genes, myc
Immunoglobulin Heavy Chains
Lymph Nodes
Mice
Mice, Inbred BALB C
Polymerase Chain Reaction
Translocation, Genetic