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¹ Laboratory of Cancer Biology and Genetics, ² Genetics Branch, Cancer Genomics Section, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892
³ Ernst-Moritz-Arndt University, D-17487 Greifswald, Germany
⁴ Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852
⁵ Department of Pathology, University of Iowa, Carver Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242
⁶ Department of Immunology and Genomic Medicine, Kyoto University, Graduate School of Medicine, Kyoto 606-8501, Japan
⁷ Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan
⁸ Genentech, Inc., South San Francisco, CA 94080

CORRESPONDENCE Michael Potter:potter{at}helix.nih.gov

Activation-induced cytidine deaminase (AID) is required for immunoglobulin (Ig) class switch recombination and somatic hypermutation, and has also been implicated in translocations between Ig switch regions and c-Myc in plasma cell tumors in mice. We asked if AID is required for accelerated tumor development in pristane-treated Bcl-xL transgenic BALB/c mice deficient in AID (pBxAicda–/–). pBxAicda^–/– mice developed tumors with a lower frequency (24 vs. 62%) and a longer mean latency (108 vs. 36 d) than AID-sufficient mice. The tumors appeared in oil granuloma tissue and did not form ascites. By interphase fluorescence in situ hybridization, six out of nine pBxAicda^–/– primary tumors had T(12;15) and one had T(6;15) chromosomal translocations. Two tumors were transplantable and established as stable cell lines. Molecular and cytogenetic analyses showed that one had an unusual unbalanced T(12;15) translocation, with IgH Cµ and Pvt-1 oriented head to tail at the breakpoint, resulting in an elevated expression of c-Myc. In contrast, the second was T(12;15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors.

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