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Title: Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers

Abstract

Purpose: To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. Methods and Materials: Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatment (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. Results: Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; <6 kb in 18% in HL patients), increased spontaneous chromosomal abnormalities, and increased in vitro radiation sensitivity (p < 10{sup -4} each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations.more » Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. Conclusions: An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [7]; ;  [2];  [7]; ; ;  [8];  [9];  [10];  [11];  [7]
  1. Laboratoire de la Radiosensibilite des Tumeurs et des Tissus Sains, UPRES EA 27-10, Institut Gustave Roussy, Villejuif (France). E-mail: mkacher@igr.fr
  2. Departement de la Biologie Clinique, Institut Gustave Roussy, Villejuif (France)
  3. Departement de Radiotherapie, Institut Gustave Roussy, Villejuif (France)
  4. Departement de Bio-Statistique, Institut Gustave Roussy, Villejuif (France)
  5. Inserm U790, Institut Gustave Roussy, Villejuif (France)
  6. (France)
  7. Laboratoire de la Radiosensibilite des Tumeurs et des Tissus Sains, UPRES EA 27-10, Institut Gustave Roussy, Villejuif (France)
  8. Departement de Medecine, Institut Gustave Roussy, Villejuif (France)
  9. Laboratoire de la Radiosensibilite des Tumeurs et des Tissus Sains, UPRES EA 27-10, Institut Gustave Roussy, Villejuif (France)|[Departement de Radiotherapie, Institut Gustave Roussy, Villejuif (France)
  10. Service d'Hematologie et de Cytogenetique, Hopital de Bicetre, Le Kremlin-Bicetre (France)
  11. Cellular Genomics of Cancer Laboratory CNRS-UMR 1599, Institut Gustave Roussy, Villejuif (France)
Publication Date:
OSTI Identifier:
20951666
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 68; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2007.01.050; PII: S0360-3016(07)00242-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHROMOSOMES; DIAGNOSIS; DNA REPAIR; IN VITRO; LYMPHOCYTES; LYMPHOMAS; PATIENTS; SENSITIVITY; TELOMERES

Citation Formats

M'kacher, Radhia, Bennaceur-Griscelli, Annelise, Girinsky, Theodore, Koscielny, Serge, Delhommeau, Francois, Laboratoire d'Immunologie Hematologie, Hopital Saint-Antoine, Universite Pierre et Marie Curie, Paris, Dossou, Julien, Violot, Dominique, Leclercq, Evelyne, Courtier, Marie Helene, Beron-Gaillard, Nadine, Assaf, Elias, Ribrag, Vincent, Carde, Patrice, Bourhis, Jean, Feneux, Daniele, Bernheim, Alain, and Parmentier, Claude. Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2007.01.050.
M'kacher, Radhia, Bennaceur-Griscelli, Annelise, Girinsky, Theodore, Koscielny, Serge, Delhommeau, Francois, Laboratoire d'Immunologie Hematologie, Hopital Saint-Antoine, Universite Pierre et Marie Curie, Paris, Dossou, Julien, Violot, Dominique, Leclercq, Evelyne, Courtier, Marie Helene, Beron-Gaillard, Nadine, Assaf, Elias, Ribrag, Vincent, Carde, Patrice, Bourhis, Jean, Feneux, Daniele, Bernheim, Alain, & Parmentier, Claude. Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers. United States. doi:10.1016/j.ijrobp.2007.01.050.
M'kacher, Radhia, Bennaceur-Griscelli, Annelise, Girinsky, Theodore, Koscielny, Serge, Delhommeau, Francois, Laboratoire d'Immunologie Hematologie, Hopital Saint-Antoine, Universite Pierre et Marie Curie, Paris, Dossou, Julien, Violot, Dominique, Leclercq, Evelyne, Courtier, Marie Helene, Beron-Gaillard, Nadine, Assaf, Elias, Ribrag, Vincent, Carde, Patrice, Bourhis, Jean, Feneux, Daniele, Bernheim, Alain, and Parmentier, Claude. Fri . "Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers". United States. doi:10.1016/j.ijrobp.2007.01.050.
@article{osti_20951666,
title = {Telomere Shortening and Associated Chromosomal Instability in Peripheral Blood Lymphocytes of Patients With Hodgkin's Lymphoma Prior to Any Treatment Are Predictive of Second Cancers},
author = {M'kacher, Radhia and Bennaceur-Griscelli, Annelise and Girinsky, Theodore and Koscielny, Serge and Delhommeau, Francois and Laboratoire d'Immunologie Hematologie, Hopital Saint-Antoine, Universite Pierre et Marie Curie, Paris and Dossou, Julien and Violot, Dominique and Leclercq, Evelyne and Courtier, Marie Helene and Beron-Gaillard, Nadine and Assaf, Elias and Ribrag, Vincent and Carde, Patrice and Bourhis, Jean and Feneux, Daniele and Bernheim, Alain and Parmentier, Claude},
abstractNote = {Purpose: To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. Methods and Materials: Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatment (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. Results: Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; <6 kb in 18% in HL patients), increased spontaneous chromosomal abnormalities, and increased in vitro radiation sensitivity (p < 10{sup -4} each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations. Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. Conclusions: An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients.},
doi = {10.1016/j.ijrobp.2007.01.050},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 68,
place = {United States},
year = {Fri Jun 01 00:00:00 EDT 2007},
month = {Fri Jun 01 00:00:00 EDT 2007}
}