title: The Use of 3D Telomere FISH for the Characterization of the Nuclear Architecture in EBV-Positive Hodgkin's Lymphoma.
abstract: The 3D nuclear architecture is closely related to cellular functions and chromosomes are organized in distinct territories. Quantitative 3D telomere FISH analysis (3D Q-FISH) and 3D super-resolution imaging (3D-SIM) at a resolution up to 80 nm as well as the recently developed combined quantitative 3D TRF2-telomere immune FISH technique (3D TRF2/Telo-Q-FISH) have substantially contributed to elucidate molecular pathogenic mechanisms of hematological diseases. Here we report the methods we applied to uncover major molecular steps involved in the pathogenesis of EBV-associated Hodgkin's lymphoma. These methods allowed us to identify the EBV-encoded oncoprotein LMP1 as a key element in the formation of Hodgkin (H-cell) and multinucleated Reed-Sternberg cells (RS-cell), the diagnostic tumor cell of classical Hodgkin's lymphoma (cHL). LMP1 mediates multinuclearity through downregulation of shelterin proteins, in particular telomere repeat binding factor 2 (TRF2).
authors.affiliation: Division of Hematology, Department of Medicine, Jewish General Hospital, McGill University, 3755, Chemin de la Côte Ste-Catherine, Montréal, Québec, Canada, H3T 1E2. hans.knecht@mcgill.ca.
authors.forename: Hans
authors.initials: H
authors.lastname: Knecht
authors.affiliation: Genomic Center for Cancer Research and Diagnosis, Cell Biology, Univeristy of Manitoba, CancerCare Manitoba, Winnipeg, MB, Canada.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000906:Antibodies / Q000276:immunology; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D035341:Telomeric Repeat Binding Protein 2; D014763:Viral Matrix Proteins
keywords: 3D Q-FISH; 3D TRF2/Telo-Q-FISH; Hodgkin cell; Hodgkin’s lymphoma; LMP1 oncoprotein; Reed-Sternberg cell; Shelterin; TRF2; Telomere; Three-dimensional (3D) imaging