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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 (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 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 Bea, S. Articles by Campo, E. Search for Related Content PubMed PubMed Citation Articles by Bea, S. Articles by Campo, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 28, 2008 Accepted October 17, 2008 Uniparental disomies, homozygous deletions, amplifications and target genes in mantle cell lymphoma revealed by integrative high-resolution whole genome profiling Silvia Bea, Itziar Salaverria, Lluis Armengol, Magda Pinyol, Veronica Fernandez, Elena M Hartmann, Pedro Jares, Virginia Amador, Luis Hernandez, Alba Navarro, German Ott, Andreas Rosenwald, Xavier Estivill, and Elias Campo* Hematopathology Unit, Department of Pathology, Hospital Clinic, (IDIBAPS), University of Barcelona, Barcelona, Spain Genes and Disease Program, Center for Genomic Regulation (CRG-UPF), (CIBERESP), Pompeu Fabra University, Barcelona, Spain Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany Institute of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany * Corresponding author; email: ecampo{at}clinic.ub.es. 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 ten 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 (UPD). The UPD at 17p was one of the most common and it was associated with TP53 gene inactivation. Homozygous deletions targeted four known tumor suppressor genes (CDKN2C, BCL2L11, CDKN2A, RB1) and six new genes (FAF1, MAP2, SP100, MOBKL2B, ZNF280A, 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, that 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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