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.

Details

Serval ID
serval:BIB_2C7EC4261439
Type
Article: article from journal or magazin.
Collection
Publications
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.
Journal
International Journal of Radiation Oncology, Biology, Physics
Author(s)
M'kacher R., Bennaceur-Griscelli A., Girinsky T., Koscielny S., Delhommeau F., Dossou J., Violot D., Leclercq E., Courtier M.H., Béron-Gaillard N., Assaf E., Ribrag V., Bourhis J., Feneux D., Bernheim A., Parmentier C., Carde P.
ISSN
0360-3016 (Print)
ISSN-L
0360-3016
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
68
Number
2
Pages
465-471
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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(-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.
Keywords
Adult, Aged, Breast Neoplasms/genetics, Carcinoma, Basal Cell/genetics, Chromosomal Instability/genetics, Cohort Studies, DNA Repair, Female, Follow-Up Studies, Hodgkin Disease/drug therapy, Hodgkin Disease/genetics, Humans, Lymphocytes/pathology, Lymphocytes/radiation effects, Male, Middle Aged, Neoplasms, Second Primary/etiology, Neoplasms, Second Primary/genetics, Prospective Studies, Radiation Tolerance, Skin Neoplasms/genetics, Survivors, Telomere/pathology
Pubmed
Web of science
Create date
01/12/2014 17:29
Last modification date
20/08/2019 13:11
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