3D Telomere FISH defines LMP1-expressing Reed- Sternberg cells as end-stage cells with telomere-poor 'ghost' nuclei and very short telomeres
Identifieur interne : 000D57 ( Main/Exploration ); précédent : 000D56; suivant : 000D583D Telomere FISH defines LMP1-expressing Reed- Sternberg cells as end-stage cells with telomere-poor 'ghost' nuclei and very short telomeres
Auteurs : Hans Knecht [Canada] ; Bassem Sawan [Canada] ; Zelda Lichtensztejn [Canada] ; Daniel Lichtensztejn [Canada] ; Sabine Mai [Canada]Source :
- Laboratory investigation [ 0023-6837 ] ; 2010.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Biotechnologie, Homme.
English descriptors
- KwdEn :
Abstract
In Epstein-Barr virus (EBV) negative Hodgkin's cell lines and classical EBV-negative Hodgkin's lymphoma (HL), Reed-Sternberg cells (RS cells) represent end-stage tumor cells, in which further nuclear division becomes impossible because of sustained telomere loss, shortening and aggregation. However, the three-dimensional (3D) telomere organization in latent membrane protein 1 (LMP1)-expressing RS cells of EBV-associated HL is not known. We performed a 3D telomere analysis after quantitative fluorescent in situ hybridization on 5 μm tissue sections on two LMP1-expressing HL cases and showed highly significant telomere shortening (P<0.0001) and formation of telomere aggregates in RS cells (P<0.0001), when compared with the mononuclear precursor Hodgkin cells (H cells). Telomere-poor or telomere-free 'ghost' nuclei were a regular finding in these RS cells. These nuclei and their telomere content strongly contrasted with the corona of surrounding lymphocytes showing numerous midsized telomere hybridization signals. Both H cells and RS cells of two EBV-negative HL cases analyzed in parallel showed 3D telomere patterns identical to those of LMP1-expressing cases. As a major advance, our 3D nuclear imaging approach allows the visualization of hitherto unknown profound changes in the 3D nuclear telomere organization associated with the transition from LMP1-positive H cells to LMP1-positive RS cells. We conclude that RS cells irrespective of LMP1 expression are end-stage tumor cells in which the extent of their inability to divide further is proportional to the increase of very short telomeres, telomere loss, aggregate formation and the generation of 'ghost' nuclei.
Affiliations:
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Manitoba</orgName></affiliation></author><author><name sortKey="Sawan, Bassem" sort="Sawan, Bassem" uniqKey="Sawan B" first="Bassem" last="Sawan">Bassem Sawan</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Département de Pathologie, CHUS, Université de Sherbrooke</s1><s2>Québec</s2><s3>CAN</s3><sZ>2 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Lichtensztejn, Zelda" sort="Lichtensztejn, Zelda" uniqKey="Lichtensztejn Z" first="Zelda" last="Lichtensztejn">Zelda Lichtensztejn</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Manitoba Institute of Cell Biology, University of Manitoba</s1><s2>Winnipeg, Manitoba</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName><orgName type="university">Université du 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type="wicri:Area/Main/Exploration">000D57</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">3D Telomere FISH defines LMP1-expressing Reed- Sternberg cells as end-stage cells with telomere-poor 'ghost' nuclei and very short telomeres</title><author><name sortKey="Knecht, Hans" sort="Knecht, Hans" uniqKey="Knecht H" first="Hans" last="Knecht">Hans Knecht</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Département de Médicine, CHUS, Université de Sherbrooke</s1><s2>Québec</s2><s3>CAN</s3><sZ>1 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Manitoba Institute of Cell Biology, University of Manitoba</s1><s2>Winnipeg, Manitoba</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName><orgName type="university">Université du Manitoba</orgName></affiliation></author><author><name sortKey="Sawan, Bassem" sort="Sawan, Bassem" uniqKey="Sawan B" first="Bassem" last="Sawan">Bassem Sawan</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Département de Pathologie, CHUS, Université de Sherbrooke</s1><s2>Québec</s2><s3>CAN</s3><sZ>2 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Lichtensztejn, Zelda" sort="Lichtensztejn, Zelda" uniqKey="Lichtensztejn Z" first="Zelda" last="Lichtensztejn">Zelda Lichtensztejn</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Manitoba Institute of Cell Biology, University of Manitoba</s1><s2>Winnipeg, Manitoba</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName><orgName type="university">Université du Manitoba</orgName></affiliation></author><author><name sortKey="Lichtensztejn, Daniel" sort="Lichtensztejn, Daniel" uniqKey="Lichtensztejn D" first="Daniel" last="Lichtensztejn">Daniel Lichtensztejn</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Manitoba Institute of Cell Biology, University of Manitoba</s1><s2>Winnipeg, Manitoba</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName><orgName type="university">Université du Manitoba</orgName></affiliation></author><author><name sortKey="Mai, Sabine" sort="Mai, Sabine" uniqKey="Mai S" first="Sabine" last="Mai">Sabine Mai</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Manitoba Institute of Cell Biology, University of Manitoba</s1><s2>Winnipeg, Manitoba</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName><orgName type="university">Université du Manitoba</orgName></affiliation></author></analytic><series><title level="j" type="main">Laboratory investigation</title><title level="j" type="abbreviated">Lab. invest.</title><idno type="ISSN">0023-6837</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Laboratory investigation</title><title level="j" type="abbreviated">Lab. invest.</title><idno type="ISSN">0023-6837</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biotechnology</term><term>Cell nucleus</term><term>Clinical biology</term><term>Epstein Barr virus</term><term>Fluorescence in situ hybridization</term><term>Hodgkin disease</term><term>Human</term><term>Latent membrane protein 1</term><term>Organization</term><term>Sternberg cell</term><term>Telomere</term><term>Terminal stage</term><term>Three dimensional space</term><term>Viral disease</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Hodgkin</term><term>Télomère</term><term>Hybridation in situ fluorescence</term><term>Cellule Sternberg</term><term>Stade terminal</term><term>Noyau cellulaire</term><term>Virus Epstein Barr</term><term>Virose</term><term>Organisation</term><term>Biologie clinique</term><term>Biotechnologie</term><term>Espace 3 dimensions</term><term>Homme</term><term>Protéine LMP1</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Biotechnologie</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In Epstein-Barr virus (EBV) negative Hodgkin's cell lines and classical EBV-negative Hodgkin's lymphoma (HL), Reed-Sternberg cells (RS cells) represent end-stage tumor cells, in which further nuclear division becomes impossible because of sustained telomere loss, shortening and aggregation. However, the three-dimensional (3D) telomere organization in latent membrane protein 1 (LMP1)-expressing RS cells of EBV-associated HL is not known. We performed a 3D telomere analysis after quantitative fluorescent in situ hybridization on 5 μm tissue sections on two LMP1-expressing HL cases and showed highly significant telomere shortening (P<0.0001) and formation of telomere aggregates in RS cells (P<0.0001), when compared with the mononuclear precursor Hodgkin cells (H cells). Telomere-poor or telomere-free 'ghost' nuclei were a regular finding in these RS cells. These nuclei and their telomere content strongly contrasted with the corona of surrounding lymphocytes showing numerous midsized telomere hybridization signals. Both H cells and RS cells of two EBV-negative HL cases analyzed in parallel showed 3D telomere patterns identical to those of LMP1-expressing cases. As a major advance, our 3D nuclear imaging approach allows the visualization of hitherto unknown profound changes in the 3D nuclear telomere organization associated with the transition from LMP1-positive H cells to LMP1-positive RS cells. We conclude that RS cells irrespective of LMP1 expression are end-stage tumor cells in which the extent of their inability to divide further is proportional to the increase of very short telomeres, telomere loss, aggregate formation and the generation of 'ghost' nuclei.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Knecht, Hans" sort="Knecht, Hans" uniqKey="Knecht H" first="Hans" last="Knecht">Hans Knecht</name></noRegion><name sortKey="Knecht, Hans" sort="Knecht, Hans" uniqKey="Knecht H" first="Hans" last="Knecht">Hans Knecht</name><name sortKey="Lichtensztejn, Daniel" sort="Lichtensztejn, Daniel" uniqKey="Lichtensztejn D" first="Daniel" last="Lichtensztejn">Daniel Lichtensztejn</name><name sortKey="Lichtensztejn, Zelda" sort="Lichtensztejn, Zelda" uniqKey="Lichtensztejn Z" first="Zelda" last="Lichtensztejn">Zelda Lichtensztejn</name><name sortKey="Mai, Sabine" sort="Mai, Sabine" uniqKey="Mai S" first="Sabine" last="Mai">Sabine Mai</name><name sortKey="Sawan, Bassem" sort="Sawan, Bassem" uniqKey="Sawan B" first="Bassem" last="Sawan">Bassem Sawan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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