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Blood, 1 January 2007, Vol. 109, No. 1, pp. 271-280. Prepublished online as a Blood First Edition Paper on September 7, 2006; DOI 10.1182/blood-2006-06-026500. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-06-026500v1 109/1/271    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 Mestre-Escorihuela, C. Articles by Martinez-Climent, J. A. Search for Related Content PubMed PubMed Citation Articles by Mestre-Escorihuela, C. Articles by Martinez-Climent, J. A. Related Collections Oncogenes and Tumor Suppressors Free Research Articles Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas Cinta Mestre-Escorihuela1, Fanny Rubio-Moscardo1, Jose A. Richter1, Reiner Siebert2, Joan Climent1, Vicente Fresquet1, Elena Beltran1, Xabier Agirre1, Isabel Marugan3, Miguel Marín3, Andreas Rosenwald4, Kei-ji Sugimoto5, Luise M. Wheat5, E. Loraine Karran5, Juan F. García6, Lydia Sanchez6, Felipe Prosper1, Louis M. Staudt7, Daniel Pinkel8, Martin J. S. Dyer5, and Jose A. Martinez-Climent1, 1 Center for Applied Medical Research (CIMA), Division of Oncology, University of Navarra, Pamplona, Spain; 2 Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel, Germany; 3 Department of Hematology and Medical Oncology, Hospital Clínico, University of Valencia, Valencia, Spain; 4 Department of Pathology, University of Würzburg, Würzburg, Germany; 5 Medical Research Council (MRC) Toxicology Unit, University of Leicester, United Kingdom; 6 Molecular Pathology Program, National Center for Oncology Research (CNIO), Madrid, Spain; 7 National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD; and 8 Cancer Research Institute, University of California San Francisco, CA Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Genomic loss is our gain Jeremy S. Abramson Blood 2007 109: 6-7. [Full Text] [PDF] This article has been cited by other articles: F. Jardin, P. Ruminy, J.-P. Kerckaert, F. Parmentier, J.-M. Picquenot, S. Quief, C. Villenet, G. Buchonnet, M. Tosi, T. Frebourg, et al. Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas Haematologica, April 1, 2008; 93(4): 543 - 550. [Abstract] [Full Text] [PDF]

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