Telomere and centromere staining followed by m-fish improves diagnosis of chromosomal instability and its clinical utility

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Radhia M’kacher, Cell Environment
  • ,
  • Bruno Colicchio, Universite de Haute Alsace
  • ,
  • Claire Borie, Institut National de la Santé et de la Recherche Médicale
  • ,
  • Steffen Junker
  • Valentine Marquet, Hopital Dupuytren
  • ,
  • Leonhard Heidingsfelder, MetaSystems GmbH
  • ,
  • Kevin Soehnlen, Cell Environment
  • ,
  • Wala Najar, Cell Environment, Universite de Haute Alsace, Institut National de la Santé et de la Recherche Médicale, Hopital Dupuytren, MetaSystems GmbH, Paris Descartes University
  • ,
  • William M. Hempel, Cell Environment
  • ,
  • Noufissa Oudrhiri, Institut National de la Santé et de la Recherche Médicale
  • ,
  • Nadège Wilhelm-Murer, Service de Génétique Groupe Hospitalier de la Région de Mulhouse et Sud Alsace Mulhouse
  • ,
  • Marguerite Miguet, Service de Génétique Groupe Hospitalier de la Région de Mulhouse et Sud Alsace Mulhouse
  • ,
  • Micheline Arnoux, Institut National de la Santé et de la Recherche Médicale
  • ,
  • Catherine Ferrapie, Institut National de la Santé et de la Recherche Médicale
  • ,
  • Wendy Kerbrat, Institut National de la Santé et de la Recherche Médicale
  • ,
  • Andreas Plesch, MetaSystems GmbH
  • ,
  • Alain Dieterlen, Universite de Haute Alsace
  • ,
  • Theodore Girinsky, CNRS
  • ,
  • Philippe Voisin, Cell Environment
  • ,
  • Georges Deschenes, Hopital Robert-Debre AP-HP
  • ,
  • Anne Claude Tabet, Hopital Robert-Debre AP-HP
  • ,
  • Catherine Yardin, Hopital Dupuytren
  • ,
  • Annelise Bennaceur-Griscelli, Institut National de la Santé et de la Recherche Médicale
  • ,
  • Michael Fenech, University of South Australia, Genome Health Foundation
  • ,
  • Patrice Carde, CNRS
  • ,
  • Eric Jeandidier, Service de Génétique Groupe Hospitalier de la Région de Mulhouse et Sud Alsace Mulhouse

Dicentric chromosomes are a relevant marker of chromosomal instability. Their appearance is associated with telomere dysfunction, leading to cancer progression and a poor clinical outcome. Here, we present Telomere and Centromere staining followed by M-FISH (TC+M-FISH) for improved detection of telomere dysfunction and the identification of dicentric chromosomes in cancer patients and various genetic syndromes. Significant telomere length shortening and significantly higher frequencies of telomere loss and deletion were found in the peripheral lymphocytes of patients with cancer and genetic syndromes relative to similar age-matched healthy donors. We assessed our technique against conventional cytogenetics for the detection of dicentric chromosomes by subjecting metaphase preparations to both approaches. We identified dicentric chromosomes in 28/50 cancer patients and 21/44 genetic syndrome patients using our approach, but only 7/50 and 12/44, respectively, using standard cytogenetics. We ascribe this discrepancy to the identification of the unique configuration of dicentric chromosomes. We observed significantly higher frequencies of telomere loss and deletion in patients with dicentric chromosomes (p < 10−4). TC+M-FISH analysis is superior to classical cytogenetics for the detection of chromosomal instability. Our approach is a relatively simple but useful tool for documenting telomere dysfunction and chromosomal instability with the potential to become a standard additional diagnostic tool in medical genetics and the clinic.

Original languageEnglish
Article number475
JournalGenes
Volume11
Issue5
ISSN2073-4425
DOIs
Publication statusPublished - May 2020

    Research areas

  • Cancer, Centromere, Chromosomal instability, Dicentric chromosome, Genetic syndrome, Telomere

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