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
05/14/2003Pubmed ID
12743607DOI
10.1038/sj.onc.1206345Scopus ID
2-s2.0-0037616590 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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 SAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsB-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