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Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas

Calame, Kathryn and Kim, Stuart and Lalley, Peter and Hill, Robert E. and Davis, Mark and Hood, Leroy (1982) Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas. Proceedings of the National Academy of Sciences of the United States of America, 79 (22). pp. 6994-6998. ISSN 0027-8424.

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Expression of IgA by plasmacytomas occurs as a result of a DNA rearrangement that brings the variable region gene, VH, a few kilobases 5' to the constant region gene, C alpha. In this study, we show that the allelic nonexpressed C alpha gene also is rearranged in most plasmacytomas. Cloning, restriction mapping, heteroduplex analyses, and sequence analyses of the nonproductively rearrange C alpha genes from two plasmacytomas, M603 and M167, have demonstrated that the nonproductive rearrangement occurs within the alpha switching region, S alpha. In each case, the same DNA sequence has been joined to the 5' side of C alpha and we have termed this DNA "NIRD" (for nonimmunoglobulin rearranged DNA). Southern blotting analyses of genomic DNAs from various IgG-, IgM-, or IgA-producing plasmacytomas suggest that NIRD is rearranged in almost all plasmacytomas. However, NIRD rearranges to the S alpha region only in IgA-producing cells, not in IgM or IgG producers. Cytogenetic evidence has shown that T(12;15) translocations are common in murine plasmacytomas. Immunoglobulin heavy chain genes are located on chromosome 12, and the translocation breakpoint in plasmacytomas occurs near the immunoglobulin genes. NIRD has been mapped to chromosome 15 by Southern blotting analysis of mouse-hamster cell lines, suggesting that the nonproductively rearranged C alpha clones represent the T(12;15) translocations identified cytogenetically. Therefore, we have identified a region of DNA on chromosome 15 that is commonly rearranged in transformed mouse lymphocytes. We speculate on the significance of NIRD in neoplastic transformation of mouse lymphocytes.

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Hood, Leroy0000-0001-7158-3678
Additional Information:© 1982 by the National Academy of Sciences. Contributed by Leroy Hood, August 17, 1982. The authors wish to thank Roy Riblet for the gift of NZB plasmacytoma DNAs and Mitch Kronenberg for the gift of T-cell hybridoma DNAs. We thank R. Wall for supplying the P3K and E1 cell lines. We thank Steve Crews, Rick Barth, Roger Perlmutter, and Barbara Wold for helpful advice and discussions. The assistance of Connie Katz, Bernita Larsh, and Kathy Kanamori in preparing the manuscript is gratefully acknowledged. This work was supported by National Institutes of Health grants to K.C. and to L.H.; S.K. and M.D. were supported by a National Institutes of Health training grant. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
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Subject Keywords:class switching; oncogenesis
Issue or Number:22
Record Number:CaltechAUTHORS:CALpnas82
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11970
Deposited By: Tony Diaz
Deposited On:16 Oct 2008 23:29
Last Modified:03 Oct 2019 00:24

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