Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32)

Johannes W.G. Janssen, Jan Willem Vaandrager, Tanja Heuser, Anna Jauch, Philip M. Kluin, Erik Geelen, P. Leif Bergsagel, W. Michael Kuehl, Hans G. Drexler, Takemi Otsuki, Claus R. Bartram, Ed Schuuring

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99 Scopus citations

Abstract

Through the application of the NIH/3T3 tumorigenicity assay to DNA from a gastric carcinoma, we have identified a novel transforming gene, designated myeov (myeloma overexpressed gene in a subset of t[11;14]-positive multiple myelomas). Sequence analyses did not reveal any homology with sequences present in the GenBank, except the deduced protein structure predicts a transmembrane localization. Myeov was mapped to chromosome 11q13 and localized by DNA fiber fluorescence in situ hybridization (FISH) 360-kilobase (kb) centromeric of cyclin D1. In 3 of 7 multiple myeloma (MM) cell lines with a t(11;14)(q13;q32) and cyclin-D1 overexpression, Northern blot analysis revealed overexpression of myeov as well. In all 7 cell lines, the translocation breakpoint was mapped within the 360-kb region between myeov and cyclin D1. DNA fiber FISH with a contig of probes covering the constant region of the immunoglobulin heavy chain (IgH) revealed that exclusively in the 3 myeov-overexpressing cell lines (KMS-12, KMS-21, and XG-5), either the 5' Eμ enhancer or the most telomeric 3' Eα enhancer was juxtaposed to myeov. Although cyclin D1 overexpression represents a characteristic feature of all MM cell lines with t(11;14), our results demonstrate aberrant expression of a second putative oncogene in a subset of these cases, due to juxtaposition to IgH enhancers. The clinical relevance of this dual activation remains to be elucidated. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2691-2698
Number of pages8
JournalBlood
Volume95
Issue number8
StatePublished - Apr 15 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Janssen, J. W. G., Vaandrager, J. W., Heuser, T., Jauch, A., Kluin, P. M., Geelen, E., Bergsagel, P. L., Kuehl, W. M., Drexler, H. G., Otsuki, T., Bartram, C. R., & Schuuring, E. (2000). Concurrent activation of a novel putative transforming gene, myeov, and cyclin D1 in a subset of multiple myeloma cell lines with t(11;14)(q13;q32). Blood, 95(8), 2691-2698.