GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma |
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| Authors: | Inga Vater Florian Wagner Markus Kreuz Hilmar Berger José I Martín-Subero Christiane Pott Jose A Martinez-Climent Wolfram Klapper Kristina Krause Martin J S Dyer Stefan Gesk Lana Harder Alberto Zamo Martin Dreyling Dirk Hasenclever Norbert Arnold Reiner Siebert |
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| Institution: | Institute of Human Genetics, Christian-Albrechts University Kiel, Kiel, Germany;, German Resource Centre for Genome Research (RZPD), Berlin, Germany;, Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany;, Second Medical Department, Christian-Albrechts University Kiel, Kiel, Germany;, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain;, Institute of Pathology, Section Haematopathology and Lymph Node Registry, Christian-Albrechts University Kiel, Kiel, Germany;, MRC Toxicology Unit, University of Leicester, Leicester, UK;, Department of Pathology, University of Verona, Verona, Italy;, Department of Medicine III, University Hospital Grosshadern/LMU, CCG Leukaemia, GSF-National Research Centre for Environment and Health, Munich, Germany;, and Department of Gynaecology and Obstetrics, Christian-Albrechts University Kiel, Kiel, Germany |
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| Abstract: | The translocation t(11;14)(q13;q32) is the genetic hallmark of mantle cell lymphoma (MCL) but is not sufficient for inducing lymphomagenesis. Here we performed genome-wide 100K GeneChip Mapping in 26 t(11;14)-positive MCL and six MCL cell lines. Partial uniparental disomy (pUPD) was shown to be a recurrent chromosomal event not only in MCL cell lines but also in primary MCL. Remarkably, pUPD affected recurrent targets of deletion like 11q, 13q and 17p. Moreover, we identified 12 novel regions of recurrent gain and loss as well as 12 high-level amplifications and eight homozygously deleted regions hitherto undescribed in MCL. Interestingly, GeneChip analyses identified different genes , encoding proteins involved in microtubule dynamics, such as MAP2 , MAP6 and TP53, as targets for chromosomal aberration in MCL. Further investigation, including mutation analyses, fluorescence in situ hybridisation as well as epigenetic and expression studies, revealed additional aberrations frequently affecting these genes. In total, 19 of 20 MCL cases, which were subjected to genetic and epigenetic analyses, and five of six MCL cell lines harboured at least one aberration in MAP2, MAP6 or TP53 . These findings provide evidence that alterations of microtubule dynamics might be one of the critical events in MCL lymphomagenesis contributing to chromosomal instability. |
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| Keywords: | mantle cell lymphoma microarray single nucleotide polymorphisms microtubule-associated proteins partial uniparental disomy |
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