Document Detail


3D Telomere FISH defines LMP1-expressing Reed-Sternberg cells as end-stage cells with telomere-poor 'ghost' nuclei and very short telomeres.
MedLine Citation:
PMID:  20142802     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 mum 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.
Authors:
Hans Knecht; Bassem Sawan; Zelda Lichtensztejn; Daniel Lichtensztejn; Sabine Mai
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-08
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  90     ISSN:  1530-0307     ISO Abbreviation:  Lab. Invest.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-30     Completed Date:  2010-05-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  611-9     Citation Subset:  IM    
Affiliation:
Division of Haematology/Oncology, CHUS University Hospital, 3001 12th Avenue North, Sherbrooke, Qu?bec, Canada. hans.knecht@usherbrooke.ca
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MeSH Terms
Descriptor/Qualifier:
Adult
Female
Hodgkin Disease / genetics*,  metabolism,  pathology*
Humans
Image Processing, Computer-Assisted
In Situ Hybridization, Fluorescence
Male
Reed-Sternberg Cells / metabolism,  pathology*
Telomere / pathology*
Viral Matrix Proteins / analysis
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/EBV-associated membrane antigen, Epstein-Barr virus; 0/Viral Matrix Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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