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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 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 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 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. Related Collections Neoplasia Cell Adhesion and Motility Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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. Martín-Subero, Inga Nieländer, Javier Garcia-Conde, Martin J. S. Dyer, Maria Jose Terol, Daniel Pinkel, and Jose A. Martinez-Climent From the Department of Hematology and Medical Oncology, Hospital Clínico, University of Valencia, Spain; Division of Oncology, Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain; Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Germany; Molecular Pathology Program, Centro Nacional de Investigaciones Oncolgógicas (CNIO), Madrid, Spain; Medical Research Council (MRC) Toxicology Unit, University of Leicester, United Kingdom; and Cancer Research Institute, University of California San Francisco, CA. To identify recurrent genomic changes in mantle cell lymphoma (MCL), we used high-resolution comparative genomic hybridization (CGH) to bacterial artificial chromosome (BAC) microarrays in 68 patients and 9 MCL-derived cell lines. Array CGH defined an 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 than nodal cases, including 8p21.3 deletion at tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor gene cluster (55% versus 19%; P = .01) and gain of 8q24.1 at MYC locus (46% versus 14%; P = .015). Additionally, leukemic MCL exhibited frequent IGVH mutation (64% versus 21%; P = .009) with preferential VH4-39 use (36% versus 4%; P = .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, while 1p21 loss was associated with prolonged survival (P = .02). In multivariate analysis, deletion of 9q21-q22 was the strongest predictor for inferior survival (hazard ratio [HR], 6; confidence interval [CI], 2.3 to 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: I. Nielander, J. I. Martin-Subero, F. Wagner, M. Baudis, S. Gesk, L. Harder, D. Hasenclever, W. Klapper, M. Kreuz, C. Pott, et al. 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