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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4445-4454. Prepublished online as a Blood First Edition Paper on February 17, 2005; DOI 10.1182/blood-2004-10-3907. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2004-10-3907v1 105/11/4445    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 Rubio-Moscardo, F. Articles by Martinez-Climent, J. A Search for Related Content PubMed PubMed Citation Articles by Rubio-Moscardo, F. Articles by Martinez-Climent, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 21, 2004 Accepted January 14, 2005 Mantle cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome Fanny Rubio-Moscardo, Joan Climent, Reiner Siebert, Miguel A Piris, Jose I Martin-Subero, Inga Nielander, Javier Garcia-Conde, Martin J Dyer, Maria J Terol, Daniel Pinkel, and Jose A Martinez-Climent* Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Valencia, Spain; Division of Oncology, Center for Applied Medical Research CIMA, University of Navarra, Pamploma, Spain Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Molecular Pathology Program, CNIO, Madrid, Spain Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Valencia, Spain MRC Toxicology Unit, University of Leicester, Leicester, United Kingdom Cancer Research Institute, University of California San Francisco, San Francisco, CA, USA * Corresponding author; email: jamcliment{at}unav.es. To identify recurrent genomic changes in mantle cell lymphoma (MCL), we used high-resolution CGH to BAC microarrays in 68 patients and 9 MCL-derived cell lines. Array-CGH defined a MCL genomic signature distinct from other B-cell lymphomas, including deletions of 1p21 and 11q22.3-ATM gene with coincident 10p12-BMI1 gene amplification and 10p14 deletion, along with a previously unidentified loss within 9q21-q22. Specific genomic alterations were associated with different subgroups of disease. Notably, 11 patients with leukemic MCL showed a different genomic profile to nodal cases, including 8p21.3 deletion at TRAIL receptor gene cluster (55 vs. 19%;p=0.01) and gain of 8q24.1 at MYC locus (46 vs. 14%;p=0.015). Additionally, leukemic MCL exhibited frequent IGVH mutation (64 vs. 21%;p=0.009) with preferential VH4-39 use (36 vs. 4%;p=0.005) and followed a more indolent clinical course. Blastoid variants, increased number of genomic gains, and deletions of P16/INK4a and TP53 genes correlated with poorer outcomes, whilst 1p21 loss was associated with prolonged survival (p=0.02). In multivariate analysis, deletion of 9q21-q22 was the strongest predictor for inferior survival (HR:6;CI:2,3-15,7). Our study highlights the genomic profile as a predictor for clinical outcome, and suggests that "genome scanning" of chromosomes 1p21, 9q21-q22, 9p21.3-P16/INK4a and 17p13.1-TP53 may be clinically useful in MCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Navarro, S. Bea, V. Fernandez, M. Prieto, I. Salaverria, P. Jares, E. Hartmann, A. Mozos, A. Lopez-Guillermo, N. Villamor, et al. MicroRNA Expression, Chromosomal Alterations, and Immunoglobulin Variable Heavy Chain Hypermutations in Mantle Cell Lymphomas Cancer Res., September 1, 2009; 69(17): 7071 - 7078. [Abstract] [Full Text] [PDF] S. 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Development of a murine model for blastoid variant mantle-cell lymphoma Blood, June 1, 2007; 109(11): 4899 - 4906. [Abstract] [Full Text] [PDF] T. Ripperger, N. von Neuhoff, K. Kamphues, M. Emura, U. Lehmann, M. Tauscher, M. Schraders, P. Groenen, B. Skawran, C. Rudolph, et al. Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle cell lymphomas Haematologica, April 1, 2007; 92(4): 460 - 468. [Abstract] [Full Text] [PDF] I. Salaverria, A. Zettl, S. Bea, V. Moreno, J. Valls, E. Hartmann, G. Ott, G. Wright, A. Lopez-Guillermo, W. C. Chan, et al. Specific Secondary Genetic Alterations in Mantle Cell Lymphoma Provide Prognostic Information Independent of the Gene Expression-Based Proliferation Signature J. Clin. Oncol., April 1, 2007; 25(10): 1216 - 1222. [Abstract] [Full Text] [PDF] J. Climent, P. Dimitrow, J. Fridlyand, J. Palacios, R. Siebert, D. G. Albertson, J. W. Gray, D. Pinkel, A. Lluch, and J. A. 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