SEARCH:   Advanced

Blood, 1 November 2005, Vol. 106, No. 9, pp. 3214-3222. Prepublished online as a Blood First Edition Paper on July 28, 2005; DOI 10.1182/blood-2005-05-2013. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-05-2013v1 106/9/3214    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 Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes Fanny Rubio-Moscardo, David Blesa, Cinta Mestre, Reiner Siebert, Theo Balasas, Adalberto Benito, Andreas Rosenwald, Joan Climent, Jose I. Martinez, Markus Schilhabel, E. Lorraine Karran, Stefan Gesk, Manel Esteller, Ronald deLeeuw, Louis M. Staudt, Jose Luis Fernandez-Luna, Daniel Pinkel, Martin J. S. Dyer, and Jose A. Martinez-Climent From the Center for Applied Medical Research (CIMA), Division of Oncology, University of Navarra, Pamplona, Spain; the Department of Hematology and Medical Oncology, Hospital Clínico, University of Valencia, and the Instituto Investigaciones Citológicas, Valencia, Spain; the Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel, Germany; the MRC Toxicology Unit, University of Leicester, United Kingdom; the Molecular Genetics Unit, Hospital Universitario Universidad Marqués de Valdecilla, Santander, Spain; the Department of Pathology, University of Würzburg, Germany; the Institute for Molecular Biotechnology, Jena, Germany; the Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; the British Columbia Cancer Agency, Vancouver, BC, Canada; the National Cancer Institute, Bethesda, MD; and the Cancer Research Institute, University of California San Francisco, CA. Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase–polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Ramalingam, J. B. Duhadaway, E. Sutanto-Ward, Y. Wang, J. Dinchuk, M. Huang, P. S. Donover, J. Boulden, L. M. McNally, A. P. Soler, et al. Bin3 Deletion Causes Cataracts and Increased Susceptibility to Lymphoma during Aging Cancer Res., March 15, 2008; 68(6): 1683 - 1690. [Abstract] [Full Text] [PDF] S. Elmore Apoptosis: A Review of Programmed Cell Death Toxicol Pathol, June 1, 2007; 35(4): 495 - 516. [Abstract] [Full Text] [PDF] G. Roue, P. Perez-Galan, M. Lopez-Guerra, N. Villamor, E. Campo, and D. Colomer Selective Inhibition of I{kappa}B Kinase Sensitizes Mantle Cell Lymphoma B Cells to TRAIL by Decreasing Cellular FLIP Level J. Immunol., February 1, 2007; 178(3): 1923 - 1930. [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. Martinez-Climent Deletion of Chromosome 11q Predicts Response to Anthracycline-Based Chemotherapy in Early Breast Cancer Cancer Res., January 15, 2007; 67(2): 818 - 826. [Abstract] [Full Text] [PDF] B. A. Walker, P. E. Leone, M. W. Jenner, C. Li, D. Gonzalez, D. C. Johnson, F. M. Ross, F. E. Davies, and G. J. Morgan Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma Blood, September 1, 2006; 108(5): 1733 - 1743. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020