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Blood, 26 March 2009, Vol. 113, No. 13, pp. 3059-3069. Prepublished online as a Blood First Edition Paper on November 4, 2008; DOI 10.1182/blood-2008-07-170183. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figure All Versions of this Article: blood-2008-07-170183v1 113/13/3059    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 Beà, S. Articles by Campo, E. Search for Related Content PubMed PubMed Citation Articles by Beà, S. Articles by Campo, E. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling Sílvia Beà1, Itziar Salaverria1, Lluís Armengol2, Magda Pinyol1, Verónica Fernández1, Elena M. Hartmann3, Pedro Jares1, Virginia Amador1, Luís Hernández1, Alba Navarro1, German Ott3,4, Andreas Rosenwald3, Xavier Estivill2, and Elias Campo1 1 Hematopathology Unit, Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; 2 Genes and Disease Program, Center for Genomic Regulation, Centro de Investigación Biomédica en Red (CIBER) in Epidemiology and Public Health and Pompeu Fabra University, Barcelona, Spain; 3 Institute of Pathology, University of Würzburg, Würzburg, Germany; and 4 Institute of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany Mantle cell lymphoma (MCL) is genetically characterized by the t(11;14)(q13;q32) translocation and a high number of secondary chromosomal alterations. However, only a limited number of target genes have been identified. We have studied 10 MCL cell lines and 28 primary tumors with a combination of a high-density single-nucleotide polymorphism array and gene expression profiling. We detected highly altered genomes in the majority of the samples with a high number of partial uniparental disomies (UPDs). The UPD at 17p was one of the most common, and it was associated with TP53 gene inactivation. Homozygous deletions targeted 4 known tumor suppressor genes (CDKN2C, BCL2L11, CDKN2A, and RB1) and 6 new genes (FAF1, MAP2, SP100, MOBKL2B, ZNF280A, and PRAME). Gene amplification coupled with overexpression was identified in 35 different regions. The most recurrent amplified regions were 11q13.3-q13.5, 13q31.3, and 18q21.33, which targeted CCND1, C13orf25, and BCL2, respectively. Interestingly, the breakpoints flanking all the genomic alterations, including UPDs, were significantly associated with genomic regions enriched in copy number variants and segmental duplications, suggesting that the recombination at these regions may play a role in the genomic instability of MCL. This integrative genomic analysis has revealed target genes that may be potentially relevant in MCL pathogenesis. 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]

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