This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Avigad, S. Articles by Yaniv, I. Search for Related Content PubMed PubMed Citation Articles by Avigad, S. Articles by Yaniv, I.

Short Telomeres: A Novel Potential Predictor of Relapse in Ewing Sarcoma

Authors' Affiliations: ¹ Molecular Oncology, Felsenstein Medical Research Center, ² Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, ³ Unit of Orthopedic Oncology, and ⁴ Pathology Department, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Requests for reprints: Smadar Avigad, Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel. Phone: 972-3937-6775; Fax: 972-3925-3042; E-mail: savigad{at}post.tau.ac.il.

Purpose: Despite advances in therapy, >50% of patients with Ewing sarcoma will relapse. The current prognostic factors are not optimal for risk prediction. Studies have shown that telomere length could predict outcome in different malignancies. Our aim was to evaluate whether telomere length could be a better prognostic factor in Ewing sarcoma and correlate the results with clinical variables, outcome, and chromosomal instability.

Experimental Design: Telomere length was determined in the primary tumor and peripheral blood of 32 patients with Ewing sarcoma. Chromosomal instability was evaluated by combining classical cytogenetics, comparative genomic hybridization and random aneuploidy. Telomere length was correlated to clinical variables, chromosomal instability, and outcome.

Results: In 75% of the tumors, changes in telomere length, when compared with the corresponding peripheral blood lymphocytes, were noted. The majority of changes consisted of a reduction in telomere length. Patients harboring shorter telomeres had a significantly adverse outcome (P = 0.015). Chromosomal instability was identified in 65% of tumors, significantly correlating with short telomeres (P = 0.0094). Using multivariate analysis, telomere length remained the only significant prognostic variable (P = 0.034). Patients with short telomeres had a 5.3-fold risk of relapse as compared to those with unchanged or longer telomeres.

Conclusion: We have shown that tumors with telomere length reduction result in genomic instability. In addition, telomere length reduction was the only significant predictor of outcome. We suggest that reduction of telomere length in tumor cells at diagnosis could serve as a prognostic marker in Ewing sarcoma.