E mu/S mu transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells

Alexander L Kovalchuk; Joong Su Kim; Siegfried Janz

doi:10.1038/sj.onc.1206345

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E mu/S mu transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells

Journal article

Peer reviewed

E mu/S mu transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells

Alexander L Kovalchuk, Joong Su Kim and Siegfried Janz

Oncogene, Vol.22(18), pp.2842-2850

05/08/2003

DOI: 10.1038/sj.onc.1206345

PMID: 12743607

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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.

Translocation, Genetic

B-Lymphocytes - physiology

Chromosome Mapping

Genes, myc

Lymph Nodes - immunology

DNA Primers

DNA Transposable Elements

Animals

Base Sequence

Polymerase Chain Reaction

Mice

Mice, Inbred BALB C

Immunoglobulin Heavy Chains - genetics

Details

Title: Subtitle: E mu/S mu transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells
Creators: Alexander L Kovalchuk - Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Joong Su Kim
Siegfried Janz
Resource Type: Journal article
Publication Details: Oncogene, Vol.22(18), pp.2842-2850
DOI: 10.1038/sj.onc.1206345
PMID: 12743607
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Language: English
Date published: 05/08/2003
Academic Unit: Pathology
Record Identifier: 9984083201002771

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