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Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma
Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF-κB activation. However, genetic alterations causing constitutive NF-κB activation are still incompletely under...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391781/ https://www.ncbi.nlm.nih.gov/pubmed/25856582 http://dx.doi.org/10.1371/journal.pone.0123922 |
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author | Troppan, Katharina Hofer, Sybille Wenzl, Kerstin Lassnig, Markus Pursche, Beata Steinbauer, Elisabeth Wiltgen, Marco Zulus, Barbara Renner, Wilfried Beham-Schmid, Christine Deutsch, Alexander Neumeister, Peter |
author_facet | Troppan, Katharina Hofer, Sybille Wenzl, Kerstin Lassnig, Markus Pursche, Beata Steinbauer, Elisabeth Wiltgen, Marco Zulus, Barbara Renner, Wilfried Beham-Schmid, Christine Deutsch, Alexander Neumeister, Peter |
author_sort | Troppan, Katharina |
collection | PubMed |
description | Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF-κB activation. However, genetic alterations causing constitutive NF-κB activation are still incompletely understood. Since A20 (TNFAIP3) is a suppressor of the NF-κB pathway and is frequently inactivated in various lymphoid malignancies, we investigated the genetic and epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3 single base pair exchanges, 2 synonymous mutations and one missense mutation were detected by direct sequencing. Gene copy number analysis revealed a reduced A20 gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical staining confirmed that A20 expression correlates with the reduction of A20 gene copy number. These data suggest that A20 contributes to tumor formation in a significant fraction of myeloma patients. |
format | Online Article Text |
id | pubmed-4391781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43917812015-04-21 Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma Troppan, Katharina Hofer, Sybille Wenzl, Kerstin Lassnig, Markus Pursche, Beata Steinbauer, Elisabeth Wiltgen, Marco Zulus, Barbara Renner, Wilfried Beham-Schmid, Christine Deutsch, Alexander Neumeister, Peter PLoS One Research Article Multiple myeloma (MM) is a malignant clonal expansion of plasma cells in the bone marrow and belongs to the mature B-cell neoplams. The pathogenesis of MM is associated with constitutive NF-κB activation. However, genetic alterations causing constitutive NF-κB activation are still incompletely understood. Since A20 (TNFAIP3) is a suppressor of the NF-κB pathway and is frequently inactivated in various lymphoid malignancies, we investigated the genetic and epigenetic properties of A20 in MM. In total, of 46 patient specimens analyzed, 3 single base pair exchanges, 2 synonymous mutations and one missense mutation were detected by direct sequencing. Gene copy number analysis revealed a reduced A20 gene copy number in 8 of 45 (17.7%) patients. Furthermore, immunohistochemical staining confirmed that A20 expression correlates with the reduction of A20 gene copy number. These data suggest that A20 contributes to tumor formation in a significant fraction of myeloma patients. Public Library of Science 2015-04-09 /pmc/articles/PMC4391781/ /pubmed/25856582 http://dx.doi.org/10.1371/journal.pone.0123922 Text en © 2015 Troppan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Troppan, Katharina Hofer, Sybille Wenzl, Kerstin Lassnig, Markus Pursche, Beata Steinbauer, Elisabeth Wiltgen, Marco Zulus, Barbara Renner, Wilfried Beham-Schmid, Christine Deutsch, Alexander Neumeister, Peter Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma |
title | Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma |
title_full | Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma |
title_fullStr | Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma |
title_full_unstemmed | Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma |
title_short | Frequent Down Regulation of the Tumor Suppressor Gene A20 in Multiple Myeloma |
title_sort | frequent down regulation of the tumor suppressor gene a20 in multiple myeloma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4391781/ https://www.ncbi.nlm.nih.gov/pubmed/25856582 http://dx.doi.org/10.1371/journal.pone.0123922 |
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