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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1120-1126. Prepublished online as a Blood First Edition Paper on April 13, 2004; DOI 10.1182/blood-2003-11-3837. This Article Full Text (PDF) All Versions of this Article: 2003-11-3837v1 104/4/1120    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Specht, K. Articles by Quintanilla-Martinez, L. Search for Related Content PubMed PubMed Citation Articles by Specht, K. Articles by Quintanilla-Martinez, L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 12, 2003 Accepted March 8, 2004 Different mechanisms of cyclin D1 overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analysis of mRNA levels Katja Specht, Eugenia Haralambieva, Karin Bink, Marcus Kremer, Sonja Mandl-Weber, Ina Koch, Raju Tomer, Heinz Hofler, Ed Schuuring, Philip M Kluin, Falko Fend, and Leticia Quintanilla-Martinez* Institute of Pathology, GSF-National Research Center for Health and Environment, Neuherberg, Germany Institute of Pathology, Technical University, Munich, Germany Institute of Pathology, University Hospital Groningen, Groningen, Netherlands Antilles Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, India Institute of Pathology, GSF-National Research Center for Health and Environment, Neuherberg, Germany; Institute of Pathology, University Hospital Groningen, Groningen, Netherlands Antilles * Corresponding author; email: quintanilla-fend{at}gsf.de. The t(11;14)(q13;q32) is the most common translocation in multiple myeloma (MM), resulting in upregulation of cyclin D1. We used a segregation fluorescent in situ hybridization (FISH) assay to detect t(11;14) breakpoints in primary MM cases and real-time RT-PCR to quantify cyclin D1 and MYEOV (myeloma overexpressed) expression, another putative oncogene located on chromosome 11q13. High levels of cyclin D1 mRNA (cyclin D1/TBP ratio >95) were found exclusively in the presence of a t(11;14) (11/48 cases; p<0.00001). In addition, a subgroup of MM cases (15/48) with intermediate to low cyclin D1 mRNA (cyclin D1/TBP ratio between 2.3 and 20) was identified. FISH analysis ruled out a t(11;14) and 11q13 amplification in these cases, however, in 13/15 patients a chromosome 11 polysomy was demonstrated (p<0.0001). These results indicate an effect of gene dosage as an alternative mechanism of cyclin D1 deregulation in MM. The absence of chromosome 11 abnormalities in 2/15 patients with intermediate cyclin D1 expression supports that there are presumably other mechanism(s) of cyclin D1 deregulation in MM patients. Our data indicate that deregulation of MYEOV is not favored in MM, and further strengthens the role of cyclin D1 overexpression in lymphoid malignancies with t(11;14)(q13;q32). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J Yeung and H Chang Genomic aberrations and immunohistochemical markers as prognostic indicators in multiple myeloma J. Clin. Pathol., July 1, 2008; 61(7): 832 - 836. [Abstract] [Full Text] [PDF] T. Bochtler, U. Hegenbart, F. W. Cremer, C. Heiss, A. Benner, D. Hose, M. Moos, J. Bila, C. R. Bartram, A. D. Ho, et al. 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Knowles, J. Lane, and S. Chen-Kiang Mutually Exclusive Cyclin-Dependent Kinase 4/Cyclin D1 and Cyclin-Dependent Kinase 6/Cyclin D2 Pairing Inactivates Retinoblastoma Protein and Promotes Cell Cycle Dysregulation in Multiple Myeloma Cancer Res., December 15, 2005; 65(24): 11345 - 11353. [Abstract] [Full Text] [PDF] L. Agnelli, S. Bicciato, M. Mattioli, S. Fabris, D. Intini, D. Verdelli, L. Baldini, F. Morabito, V. Callea, L. Lombardi, et al. Molecular Classification of Multiple Myeloma: A Distinct Transcriptional Profile Characterizes Patients Expressing CCND1 and Negative for 14q32 Translocations J. Clin. Oncol., October 10, 2005; 23(29): 7296 - 7306. [Abstract] [Full Text] [PDF] P. L. Bergsagel, W. M. Kuehl, F. Zhan, J. Sawyer, B. Barlogie, and J. Shaughnessy Jr Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma Blood, July 1, 2005; 106(1): 296 - 303. [Abstract] [Full Text] [PDF] T. Sanda, S. Iida, H. Ogura, K. Asamitsu, T. Murata, K. B. Bacon, R. 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