Three-dimensional nuclear telomere architecture is associated with differential time to progression and overall survival in glioblastoma patients

Macoura Gadji, David Fortin, Ana Maria Tsanaclis, Yuval Garini, Nir Katzir, Yifat Wienburg, Ju Yan, Ludger Klewes, Thomas Klonisch, Régen Drouin, Sabine Mai

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The absence of biological markers allowing for the assessment of the evolution and prognosis of glioblastoma (GBM) is a major impediment to the clinical management of GBM patients. The observed variability in patients' treatment responses and in outcomes implies biological heterogeneity and the existence of unidentified patient categories. Here, we define for the first time three GBM patient categories with distinct and clinically predictive three-dimensional nuclear-telomeric architecture defined by telomere number, size, and frequency of telomeric aggregates. GBM patient samples were examined by three-dimensional fluorescent in situ hybridization of telomeres using two independent three-dimensional telomere-measurement tools (TeloView program [P1] and SpotScan system [P2]). These measurements identified three patients categories (categories 1-3), displaying significant differences in telomere numbers/nucleus (P1 = .0275; P2 ≤ .0001), telomere length (P1 and P2 = .0275), and number of telomeric aggregates (P1 = .0464; P2 ≤ .0001). These categories corresponded to patients with long-term, intermediate, and short-term survival, respectively (P = .0393). The time to progression analyses showed significant differences between the three categories (P = .0167). There was a correlation between time to progression, median survival, and nuclear telomere architecture. Our study suggests a link between patient outcome and three-dimensional nuclear-telomere organization and highlights the potential clinical power of telomere signatures as a new prognostic, predictive, and potentially pharmacodynamic biomarker in GBM. Furthermore, novel automated three-dimensional high-throughput scanning as developed here permits to obtain data from 300 nuclei in 20 minutes. This method is applicable to any cell type and scanning application.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
Issue number2
StatePublished - Feb 2010

Bibliographical note

Funding Information:
Address all correspondence to: Dr. Sabine Mai, Manitoba Institute of Cell Biology, 675 McDermot Ave, Winnipeg, Manitoba, Canada R3E 0V9. E-mail: or Dr. Régen Drouin, Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001 12th Ave N, Sherbrooke, Quebec, Canada J1H 5N4. E-mail: 1M.G. was supported by a short-term fellowship under the Canadian Institutes of Health Research Strategic Training Program “Innovative Technologies in Multidisciplinary Health Research Training” (S.M.). The study was partly supported by the CancerCare Manitoba Foundation to S.M. D.F. holds the National Bank of Canada Chair for the Treatment of Brain Cancer. T.K. acknowledges the financial support from the Natural Sciences and Engineering Research Council of Canada and the Manitoba Health Research Council. R.D. holds a Canada Research Chair in Genetics, Mutagenesis, and Cancer. S.M. is the Director of the Genomic Centre for Cancer Research and Diagnosis. Received 9 October 2009; Revised 16 November 2009; Accepted 23 November 2009 Copyright © 2010 Neoplasia Press, Inc. All rights reserved 1522-8002/10/$25.00 DOI 10.1593/neo.91752


Dive into the research topics of 'Three-dimensional nuclear telomere architecture is associated with differential time to progression and overall survival in glioblastoma patients'. Together they form a unique fingerprint.

Cite this