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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2119. This Article Full Text (PDF) All Versions of this Article: 2002-07-2119v1 101/8/3109    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 Martinez-Climent, J. A Articles by Lossos, I. S Search for Related Content PubMed PubMed Citation Articles by Martinez-Climent, J. A Articles by Lossos, I. S Social Bookmarking                   What's this? Submitted July 23, 2002 Accepted October 16, 2002 Transformation of follicular lymphoma to diffuse large cell lymphoma is associated with a heterogeneous set of DNA copy number and gene expression alterations Jose A Martinez-Climent*, Ash A Alizadeh, Richard Segraves, David Blesa, Fanny Rubio-Moscardo, Donna G Albertson, Javier Garcia-Conde, Martin J S Dyer, Ronald Levy, Daniel Pinkel, and Izidore S Lossos Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Valencia, Spain Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA, USA Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA Cancer Research Institute, University of California San Francisco, San Francisco, CA, USA Department of Haematology, University of Leicester, Leicester, United Kingdom * Corresponding author; email: martinez_jos{at}gva.es. Genomic aberrations in a series of paired biopsy samples from patients who presented initially with follicle center lymphoma (FCL) and subsequently transformed to diffuse large B-cell lymphoma (DLBCL) were measured by array CGH. The consequences of these aberrations on gene expression were determined by comparison with expression analysis on these specimens using cDNA microarrays. A heterogeneous pattern of acquired genomic abnormalities was observed upon transformation, some of which were recurrent in small subsets of patients. A number of the genomic aberration acquired upon transformation, such as gain/amplification of 1q21-q24, 2p16 (REL/BCL11A gene loci), 3q27-q29 (including the BCL6 locus), 7q11.2-q22.1, 12pter-q12, 18q21 (including the BCL2 locus) and Xq, and deletion of 6q22-q24, 13q14-q21 and 17p13 (P53 locus) have been previously implicated in the FCL/DLBCL pathogenesis. In addition, novel genomic imbalances not previously reported in association with FCL transformation, such as over-representation of 4p12-pter, 5p12-p15, 6p12.3-p21, 9p23, 9q13-q31, 16q, 17q21, and loss of 1p36.3, 4q21-q23, 5q21-q23, 9q31-qter, 11q24-q25 and 15q23, were identified. We observed a differential expression profile of many genes within regions of gain and deletion upon transformation, including novel target genes associated with FCL transformation. However, other genes did not show deregulated expression despite their location within these areas. In summary, the combination of array CGH and expression analysis provides a more comprehensive picture of the transformation of FCL to DLBCL. This process is associated with the acquisition of a variable spectrum of genomic imbalances affecting recurrent chromosomal areas that harbor over- or under-expressed genes targeted upon transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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