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Higher incidence of the SNP Met 788 Ile in the coding region of A20 in diffuse large B cell lymphomas

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Tumor Biology

Abstract

Genetic alterations causing constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway has been associated with the development of lymphomas. A20 (TNFAIP3) is a key regulator of NF-κB signaling. Its suppressor functions are often inactivated by deletions and/or mutations in various hematologic malignancies. Since we recently found the rs143002189 polymorphism in the A20 loci in our multiple myeloma samples, we further investigated this polymorphism in different lymphoid neoplasias. For this purpose, we tested 479 cases of the most common B cell malignancies for the presence of the rs143002189 polymorphism. We found a significant higher occurrence of the rs143002189 polymorphism in diffuse large B cell lymphoma (DLBCL) compared to non-neoplastic controls and other types of B cell malignancies. Furthermore, structure analyses of the mutated A20 protein led to the assumption that the new steric interaction within the protein is responsible for a reduced or inactivated A20 protein. Our data indicates that in a significant fraction of patients, rs143002189 might contribute to the development of DLBCL.

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Acknowledgments

This work was supported by grants from the Fellinger Krebsforschung, Land Steiermark, Hygienefond, and Jubilaeumsfond der OENB and by the START-Funding-Program of the Medical University of Graz and the City of Graz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    Authors and Affiliations

    1. Division of Hematology, Department of Internal Medicine, Medical University of Graz Austria, Graz, Austria

      Kerstin Wenzl, Sybille Hofer, Katharina Troppan, Markus Lassnig, Peter Neumeister & Alexander Deutsch

    2. Institute of Pathology, Medical University of Graz Austria, Graz, Austria

      Elisabeth Steinbauer & Christine Beham-Schmid

    3. Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz Austria, Graz, Austria

      Marco Wiltgen

    4. Division of Medical and Chemical Laboratory Diagnostics, Medical University of Graz Austria, Graz, Austria

      Barbara Zulus & Wilfried Renner

    Authors
    1. Kerstin Wenzl
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    2. Sybille Hofer
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    5. Elisabeth Steinbauer
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    11. Alexander Deutsch
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    Correspondence to Alexander Deutsch.

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    Kerstin Wenzl, Sybille Hofer, Katharina Troppan, Peter Neumeister and Alexander Deutsch contributed equally to this work.

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    Wenzl, K., Hofer, S., Troppan, K. et al. Higher incidence of the SNP Met 788 Ile in the coding region of A20 in diffuse large B cell lymphomas. Tumor Biol. 37, 4785–4789 (2016). https://doi.org/10.1007/s13277-015-4322-1

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