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| |  Consensus Regions and Novel Recurrent Amplifications Point to Genomic Regions of Interest in High-Grade Non-Hodgkin's Lymphomas: Presented at ICML By Chris Berrie LUGANO, SWITZERLAND -- June 13, 2005 -- Consensus regions for chromosomal losses and gains and novel recurrent amplifications between diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), and Burkitt-like lymphoma (BLL) suggest common genetic regions of interest for new paradigms of disease classification, clinical course, and treatment choice. Researchers reported these findings from a multicentre retrospective analysis of aggressive non-Hodgkin's lymphoma (NHL) here on June 9th at the 9th International Conference on Malignant Lymphoma (ICML). Swen Wessendorf, MD, principal investigator and medical researcher, Innere Medizin III, Medizinische Klinik der Universtiät, Ulm, Germany, reported the results on behalf of the Molecular Mechanisms in Malignant Lymphoma Network (MMML-N). Morphological, immunological, and especially more recent genetic studies have shown that DLBCL is not a single-disease entity. Therefore, Dr Wessendorf and colleagues focused their high-resolution array-based comparative genomic hybridisation analysis in particular on the potential chromosome aberrations and imbalances that might aid in the morphological and molecular distinction between typical and atypical BLs and DLBCLs. From an initial 250 DLBCL samples that the reference panel of pathologists in the MMML-N reviewed, 185 that could be ascribed to aggressive B-cell NHL entered the analysis. According to the morphological criteria of the World Health Organisation classification, these were the DLBCL (n = 121) forms of: centroblastic (n = 71), immunoblastic (n = 14), and "not otherwise specified" (n = 36). Similarly, the "Burkitt lymphoma" samples (n = 33) were classified according to true Burkitt lymphoma (BL; n = 10) and Burkitt-like lymphoma (BLL; n = 23). The remaining samples classified as "Others" (n = 31) included the following: primary mediastinal B-cell lymphoma (PMBL; n = 7); DLBCL/follicular lymphoma (n = 7); follicular lymphoma I-III (FL; n = 3); DLBCL/plasmoblastic (n = 2); T-NHL (n = 1); and no panel diagnosis (n = 11). The genomic DNA chip for the initial analysis was set up using a genome-wide set of 1500 target clones selected from the "golden path" clone set, 600 contigs covering chromosomal regions known to be altered in B-cell lymphomas, and 699 selected oncogenes and tumour suppressor genes potentially relevant in B-cell neoplasms. Overall, this represented approximately 10% of the human genome with a resolution of around 1.5 Mbp. A total of 1483 chromosome aberrations were revealed, with complexities (as aberrations/case) that showed significant separation of BL (1.9; vs DLBCL; P <.001) and BLL (4.8; vs DLBCL; P <.001) from DLBCL (9.0). Among the locations of the range of genomic losses and gains detected, these were mainly represented on chromosomes 6q and 1q (32.4%, 31.9%), respectively, while chromosome region 18q21 showed the highest level of amplification (4.9%). When comparing the distributions of these chromosomal aberrations across the histological classifications, this separation of BL and BLL from DLBCL was maintained, with BL showing the absence of, and BLL a general reduction in, a number of chromosomal aberrations that were present in the wider complexities of DLBCL, including losses (17p, 9p, 1p, 13q, and 15q) and gains (18q, 12q, 7p, Xp, and 2p). However, there was also specific overlap between these DLBCL and BL/BLL chromosomal imbalances that concentrated around specific chromosomal translocations, Dr. Wessendorf said. This was seen in particular with the pattern of chromosomal imbalances of t(MYC-Ig)-positive DLBCL, which shared certain similarities with both BL and BLL lymphomas. Therefore, while BL and BLL are seen to be associated with less complex genomic alterations and aberrations, Dr Wessendorf indicated that there are also consensus regions and novel recurrent amplifications that point to genomic regions of particular interest for the future.
[Study title: High-Resolution Genomic Profiling in 185 High-Grade Non-Hodgkin's Lymphomas Using Array-Based Comparative Genomic Hybridisation. Abstract 025]
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