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Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma
Members of the nuclear factor (NF)-κB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-κB (IκB) family, whose degradation activa...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195754/ https://www.ncbi.nlm.nih.gov/pubmed/10637284 |
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author | Jungnickel, Berit Staratschek-Jox, Andrea Bräuninger, Andreas Spieker, Tilmann Wolf, Jürgen Diehl, Volker Hansmann, Martin-Leo Rajewsky, Klaus Küppers, Ralf |
author_facet | Jungnickel, Berit Staratschek-Jox, Andrea Bräuninger, Andreas Spieker, Tilmann Wolf, Jürgen Diehl, Volker Hansmann, Martin-Leo Rajewsky, Klaus Küppers, Ralf |
author_sort | Jungnickel, Berit |
collection | PubMed |
description | Members of the nuclear factor (NF)-κB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-κB (IκB) family, whose degradation activates NF-κB in response to diverse stimuli. In Hodgkin's lymphoma (HL), high constitutive nuclear activity of NF-κB is characteristic of the malignant Hodgkin and Reed-Sternberg (H/RS) cells, which occur at low number in a background of nonneoplastic inflammatory cells. In single H/RS cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IκBα gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a viral oncogene may account for NF-κB activation). There was no evidence for IκBα mutations in two non-HL entities or in normal germinal center B cells. This study establishes deleterious IκBα mutations as the first recurrent genetic defect found in H/RS cells, indicating a role of IκBα defects in the pathogenesis of HL and implying that IκBα is a tumor suppressor gene. |
format | Text |
id | pubmed-2195754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21957542008-04-16 Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma Jungnickel, Berit Staratschek-Jox, Andrea Bräuninger, Andreas Spieker, Tilmann Wolf, Jürgen Diehl, Volker Hansmann, Martin-Leo Rajewsky, Klaus Küppers, Ralf J Exp Med Brief Definitive Report Members of the nuclear factor (NF)-κB family of transcription factors play a crucial role in cellular activation, immune responses, and oncogenesis. In most cells, they are kept inactive in the cytosol by complex formation with members of the inhibitor of NF-κB (IκB) family, whose degradation activates NF-κB in response to diverse stimuli. In Hodgkin's lymphoma (HL), high constitutive nuclear activity of NF-κB is characteristic of the malignant Hodgkin and Reed-Sternberg (H/RS) cells, which occur at low number in a background of nonneoplastic inflammatory cells. In single H/RS cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IκBα gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a viral oncogene may account for NF-κB activation). There was no evidence for IκBα mutations in two non-HL entities or in normal germinal center B cells. This study establishes deleterious IκBα mutations as the first recurrent genetic defect found in H/RS cells, indicating a role of IκBα defects in the pathogenesis of HL and implying that IκBα is a tumor suppressor gene. The Rockefeller University Press 2000-01-17 /pmc/articles/PMC2195754/ /pubmed/10637284 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Jungnickel, Berit Staratschek-Jox, Andrea Bräuninger, Andreas Spieker, Tilmann Wolf, Jürgen Diehl, Volker Hansmann, Martin-Leo Rajewsky, Klaus Küppers, Ralf Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma |
title | Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma |
title_full | Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma |
title_fullStr | Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma |
title_full_unstemmed | Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma |
title_short | Clonal Deleterious Mutations in the Iκbα Gene in the Malignant Cells in Hodgkin's Lymphoma |
title_sort | clonal deleterious mutations in the iκbα gene in the malignant cells in hodgkin's lymphoma |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195754/ https://www.ncbi.nlm.nih.gov/pubmed/10637284 |
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