title: The three-dimensional organization of telomeres in the nucleus of mammalian cells.
abstract: BACKGROUND
  The observation of multiple genetic markers in situ by optical microscopy and their relevance to the study of three-dimensional (3D) chromosomal organization in the nucleus have been greatly developed in the last decade. These methods are important in cancer research because cancer is characterized by multiple alterations that affect the modulation of gene expression and the stability of the genome. It is, therefore, essential to analyze the 3D genome organization of the interphase nucleus in both normal and cancer cells.
  
  
  RESULTS
  We describe a novel approach to study the distribution of all telomeres inside the nucleus of mammalian cells throughout the cell cycle. It is based on 3D telomere fluorescence in situ hybridization followed by quantitative analysis that determines the telomeres' distribution in the nucleus throughout the cell cycle. This method enables us to determine, for the first time, that telomere organization is cell-cycle dependent, with assembly of telomeres into a telomeric disk in the G2 phase. In tumor cells, the 3D telomere organization is distorted and aggregates are formed.
  
  
  CONCLUSIONS
  The results emphasize a non-random and dynamic 3D nuclear telomeric organization and its importance to genomic stability. Based on our findings, it appears possible to examine telomeric aggregates suggestive of genomic instability in individual interphase nuclei and tissues without the need to examine metaphases. Such new avenues of monitoring genomic instability could potentially impact on cancer biology, genetics, diagnostic innovations and surveillance of treatment response in medicine.
authors.affiliation: Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada. tcychuang@hotmail.com
authors.forename: Tony Chih Yuan
authors.initials: TC
authors.lastname: Chuang
authors.forename: Sharareh
authors.initials: S
authors.lastname: Moshir
authors.forename: Yuval
authors.initials: Y
authors.lastname: Garini
authors.forename: Alice Ya-Chun
authors.initials: AY
authors.lastname: Chuang
authors.forename: Ian T
authors.initials: IT
authors.lastname: Young
authors.forename: Bart
authors.initials: B
authors.lastname: Vermolen
authors.forename: Richard
authors.initials: R
authors.lastname: van den Doel
authors.forename: Virginie
authors.initials: V
authors.lastname: Mougey
authors.forename: Mathilde
authors.initials: M
authors.lastname: Perrin
authors.forename: Martina
authors.initials: M
authors.lastname: Braun
authors.forename: Paul Donald
authors.initials: PD
authors.lastname: Kerr
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.forename: Petra
authors.initials: P
authors.lastname: Boukamp
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle; D002467:Cell Nucleus; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods*; D017403:In Situ Hybridization; D007399:Interphase; D051379:Mice; D008807:Mice, Inbred BALB C; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism