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Blood, 15 December 2005, Vol. 106, No. 13, pp. 4315-4321. Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2005-04-1753. This Article Full Text Full Text (PDF) Supplemental Figure and Table All Versions of this Article: 2005-04-1753v1 106/13/4315    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Fu, K. Articles by Chan, W. C. Search for Related Content PubMed PubMed Citation Articles by Fu, K. Articles by Chan, W. C. Related Collections Neoplasia Cell Cycle Gene Expression Genomics Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Cyclin D1–negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling Kai Fu, Dennis D. Weisenburger, Timothy C. Greiner, Sandeep Dave, George Wright, Andreas Rosenwald, Michael Chiorazzi, Javeed Iqbal, Stefan Gesk, Reiner Siebert, Daphne De Jong, Elaine S. Jaffe, Wyndham H. Wilson, Jan Delabie, German Ott, Bhavana J. Dave, Warren G. Sanger, Lynette M. Smith, Lisa Rimsza, Rita M. Braziel, H. Konrad Müller-Hermelink, Elias Campo, Randy D. Gascoyne, Louis M. Staudt, Wing C. Chan, for the Lymphoma/Leukemia Molecular Profiling Project From the Departments of Pathology and Microbiology, Preventive and Societal Medicine, and the Human Genetics Laboratory, University of Nebraska Medical Center, Omaha, NE; the Metabolism Branch, and Sections of Hematopathology and Lymphoma Clinical Research, Center for Cancer Research, and the Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD; the Department of Pathology, University of Würzburg, Würzburg, Germany; the Institute of Human Genetics, University Hospital Schleswig Holstein, Kiel, Germany; the Department of Pathology, The Netherlands Cancer Institute/Antoni von Leevenhoek Hospital, Amsterdam, the Netherlands; the Department of Pathology, Norwegian Radium Hospital, Oslo, Norway; the Department of Pathology, University of Arizona Health Sciences Center, Tucson, AZ; the Department of Pathology, University of Oregon Health Sciences Center, Portland, OR; the Department of Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain; and the Department of Pathology, British Columbia Cancer Agency, Vancouver, BC. Cyclin D1 overexpression is believed to be essential in the pathogenesis of mantle cell lymphoma (MCL). Hence, the existence of cyclin D1-negative MCL has been controversial and difficult to substantiate. Our previous gene expression profiling study identified several cases that lacked cyclin D1 expression, but had a gene expression signature typical of MCL. Herein, we report the clinical, pathologic, and genetic features of 6 cases of cyclin D1-negative MCL. All 6 cases exhibited the characteristic morphologic features and the unique gene expression signature of MCL but lacked the t(11;14)(q13; q32) by fluorescence in situ hybridization (FISH) analysis. The tumor cells also failed to express cyclin D1 protein, but instead expressed either cyclin D2 (2 cases) or cyclin D3 (4 cases). There was good correlation between cyclin D protein expression and the corresponding mRNA expression levels by gene expression analysis. Using interphase FISH, we did not detect chromosomal translocations or amplifications involving CCND2 and CCND3 loci in these cases. Patients with cyclin D1-negative MCL were similar clinically to those with cyclin D1-positive MCL. In conclusion, cases of cyclin D1-negative MCL do exist and are part of the spectrum of MCL. Up-regulation of cyclin D2 or D3 may substitute for cyclin D1 in the pathogenesis of MCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Liu, J. Huang, J. Wang, S. Jiang, A. S. Bailey, D. C. Goldman, M. Welcker, V. Bedell, M. L. Slovak, B. Clurman, et al. Transvection mediated by the translocated cyclin D1 locus in mantle cell lymphoma J. Exp. Med., July 14, 2008; (2008) jem.20072102. [Abstract] [Full Text] [PDF] N. A. Johnson and R. D. Gascoyne Gene expression signatures in follicular lymphoma: are they ready for the clinic? Haematologica, July 1, 2008; 93(7): 982 - 987. [Full Text] [PDF] K E Hunt, K K Reichard, and C S Wilson Mantle cell lymphoma lacking the t(11;14) translocation: a case report and brief review of the literature J. Clin. Pathol., July 1, 2008; 61(7): 869 - 870. [Abstract] [Full Text] [PDF] I. Wlodarska, D. Dierickx, V. Vanhentenrijk, K. Van Roosbroeck, H. Pospisilova, F. Minnei, G. Verhoef, J. Thomas, P. Vandenberghe, and C. De Wolf-Peeters Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas Blood, June 15, 2008; 111(12): 5683 - 5690. [Abstract] [Full Text] [PDF] C. Herens, F. Lambert, L. Quintanilla-Martinez, B. Bisig, C. Deusings, and L. de Leval Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression Blood, February 1, 2008; 111(3): 1745 - 1746. [Full Text] [PDF] R Sinharay, T Watanabe, H Hirono, K Hasegawa, K Soga, K Shibasaki, and Y Endo Chemotherapy for mantle cell lymphoma * Authors' reply Gut, October 1, 2007; 56(10): 1479 - 1480. 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Siebert A chromosomal translocation in cyclin D1-negative/cyclin D2-positive mantle cell lymphoma fuses the CCND2 gene to the IGK locus Blood, August 1, 2006; 108(3): 1109 - 1110. [Full Text] [PDF]

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