Journal article
AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements
The Journal of experimental medicine, Vol.204(12), pp.2989-3001
11/26/2007
DOI: 10.1084/jem.20070882
PMCID: PMC2118515
PMID: 17998390
Abstract
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.
Details
- Title: Subtitle
- AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements
- Creators
- Alexander L Kovalchuk - Laboratory of Cancer Biology and Genetics, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852Wendy duBois - Laboratory of Cancer Biology and GeneticsElizabeth Mushinski - Laboratory of Cancer Biology and GeneticsNicole E McNeil - Genetics Branch, Cancer Genomics Section, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892Carsten Hirt - Laboratory of Cancer Biology and Genetics, Ernst-Moritz-Arndt University, D-17487 Greifswald, GermanyChen-Feng Qi - Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852Zhaoyang Li - Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852Siegfried Janz - Laboratory of Cancer Biology and Genetics, Department of Pathology, University of Iowa, Carver Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242Tasuku Honjo - Department of Immunology and Genomic Medicine, Kyoto University, Graduate School of Medicine, Kyoto 606-8501, JapanMasamichi Muramatsu - Department of Molecular Genetics, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, JapanThomas Ried - Genetics Branch, Cancer Genomics Section, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892Timothy Behrens - Genentech, Inc., South San Francisco, CA 94080Michael Potter - Laboratory of Cancer Biology and Genetics
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.204(12), pp.2989-3001
- DOI
- 10.1084/jem.20070882
- PMID
- 17998390
- PMCID
- PMC2118515
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 11/26/2007
- Academic Unit
- Pathology
- Record Identifier
- 9984083262802771
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