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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 (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 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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2006 Accepted August 16, 2006 Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas Cinta Mestre-Escorihuela, Fanny Rubio-Moscardo, Jose A Richter, Reiner Siebert, Joan Climent, Vicente Fresquet, Elena Beltran, Xabier Agirre, Isabel Marugan, Miguel Marin, Andreas Rosenwald, Kei-Ji Sugimoto, Luise M Wheat, E Loraine Karran, Juan F Garcia, Lydia Sanchez, Felipe Prosper, Louis M Staudt, Daniel Pinkel, Martin JS Dyer, and Jose A Martinez-Climent* Center for Applied Medical Research, Division of Oncology, University of Navarra, Pamplona, Spain Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel, Germany Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Spain Department of Pathology, University of Wurzburg, Germany MRC Toxicology Unit, University of Leicester, UK Molecular Pathology Program, National Center for Oncology Research (CNIO, Madrid, Spain) National Cancer Institute, NIH, Bethesda, MD, USA Cancer Research Institute, University of California San Francisco, CA, USA Center for Applied Medical Research, University of Navarra, Pamplona, Spain * Corresponding author; email: jamcliment{at}unav.es. 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 twenty homozygous deletions at seven 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 pro-apoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the pro-apoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma and the INK4c/P18 was silenced by bi-allelic 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]

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