From www.bloodjournal.org by on January 26, 2011. For personal use only.

2009 113: 3059-3069 Prepublished online Nov 4, 2008; doi:10.1182/blood-2008-07-170183 Uniparental disomies, homozygous deletions, amplifications, and target in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling

Sílvia Beà, Itziar Salaverria, Lluís Armengol, Magda Pinyol, Verónica Fernández, Elena M. Hartmann, Pedro Jares, Virginia Amador, Luís Hernández, Alba Navarro, German Ott, Andreas Rosenwald, Xavier Estivill and Elias Campo

Updated information and services can be found at: http://bloodjournal.hematologylibrary.org/cgi/content/full/113/13/3059 Articles on similar topics may be found in the following Blood collections: Lymphoid Neoplasia (618 articles)

Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/misc/rights.dtl#repub_requests

Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/misc/rights.dtl#reprints

Information about subscriptions and ASH membership may be found online at: http://bloodjournal.hematologylibrary.org/subscriptions/index.dtl

Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved. From www.bloodjournal.org by on January 26, 2011. For personal use only. LYMPHOID NEOPLASIA

Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling

Sílvia Bea`,1 Itziar Salaverria,1 Lluís Armengol,2 Magda Pinyol,1 Vero´nica Ferna´ndez,1 Elena M. Hartmann,3 Pedro Jares,1 Virginia Amador,1 Luís Herna´ndez,1 Alba Navarro,1 German Ott,3,4 Andreas Rosenwald,3 Xavier Estivill,2 and Elias Campo1

1Hematopathology Unit, Department of Pathology, Hospital Clinic, Institut d’Investigacions Biome`diques August Pi i Sunyer, University of Barcelona, Barcelona, Spain; 2Genes and Disease Program, Center for Genomic Regulation, Centro de Investigacio´n Biome´dica en Red (CIBER) in Epidemiology and Public Health and Pompeu Fabra University, Barcelona, Spain; 3Institute of Pathology, University of Wu¨rzburg, Wu¨rzburg, Germany; and 4Institute of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany

Mantle cell lymphoma (MCL) is geneti- The UPD at 17p was one of the most breakpoints flanking all the genomic alter- cally characterized by the t(11;14)(q13; common, and it was associated with TP53 ations, including UPDs, were signifi- q32) translocation and a high number of inactivation. Homozygous deletions cantly associated with genomic regions secondary chromosomal alterations. targeted 4 known tumor suppressor genes enriched in copy number variants and However, only a limited number of target (CDKN2C, BCL2L11, CDKN2A, and RB1) segmental duplications, suggesting that genes have been identified. We have stud- and 6 new genes (FAF1, MAP2, SP100, the recombination at these regions may ied 10 MCL cell lines and 28 primary MOBKL2B, ZNF280A, and PRAME). Gene play a role in the genomic instability of tumors with a combination of a high- amplification coupled with overexpres- MCL. This integrative genomic analysis density single-nucleotide polymorphism sion was identified in 35 different regions. has revealed target genes that may be array and gene expression profiling. We The most recurrent amplified regions were potentially relevant in MCL pathogenesis. detected highly altered genomes in the 11q13.3-q13.5, 13q31.3, and 18q21.33, (Blood. 2009;113:3059-3069) majority of the samples with a high num- which targeted CCND1, C13orf25, and ber of partial uniparental disomies (UPDs). BCL2, respectively. Interestingly, the Introduction

M