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  • Oncogenomics
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Eμ/Sμ transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells

Oncogene volume 22, pages 2842–2850 (2003)Cite this article

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′-Cα 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, Eμ, and a truncated switch μ region, Sμ, were found in the first intron of Myc in lymph node cells of IL-6 transgenic BALB/c mice. In two cases Eμ/Sμ transposition primed Myc to get involved in apparent trans-chromosomal CSR to Cγ1, presumably leading to T(12;15). Translocations preceded by Eμ/Sμ 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 Eμ/Sμ 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′-Cα enhancer, which appears to be required for deregulating Myc in a manner that is conducive to PCT development.

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Abbreviations

CSR:

class switch recombination

Ig:

immunoglobulin

IgH :

Ig heavy-chain gene complex

PCT(s):

plasmacytoma(s)

S :

Ig switch regio

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Acknowledgements

We are grateful to Drs Michael Potter, NCI, Bethesda, MD, USA and Tadamitsu Kishimoto, Osaka University, Japan for providing BALB/c.IL-6 congenic mice and the parental C57BL/6.H2-Ld-IL-6 transgenic mice, respectively. We thank the staff of our mouse colony, particularly Tina Wellington, Lisa Craig-Davis, and Wendy DuBois, for supporting this study, and Walter Schlapkohl and the NCI CCR Fellows Editorial Board for reading the manuscript and helpful editorial suggestions.

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  1. Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Alexander L Kovalchuk, Joong Su Kim & Siegfried Janz

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  1. Alexander L Kovalchuk
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Correspondence to Siegfried Janz.

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Kovalchuk, A., Kim, J. & Janz, S. Eμ/Sμ transposition into Myc is sometimes a precursor for T(12;15) translocation in mouse B cells. Oncogene 22, 2842–2850 (2003). https://doi.org/10.1038/sj.onc.1206345

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