title: Short telomeres: a novel potential predictor of relapse in Ewing sarcoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petach Tikva, Israel. savigad@post.tau.ac.il
authors.forename: Smadar
authors.initials: S
authors.lastname: Avigad
authors.forename: Inna
authors.initials: I
authors.lastname: Naumov
authors.forename: Anat
authors.initials: A
authors.lastname: Ohali
authors.forename: Marta
authors.initials: M
authors.lastname: Jeison
authors.forename: Gili Halevy
authors.initials: GH
authors.lastname: Berco
authors.forename: Jacques
authors.initials: J
authors.lastname: Mardoukh
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.forename: Shifra
authors.initials: S
authors.lastname: Ash
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Cohen
authors.forename: Isaac
authors.initials: I
authors.lastname: Meller
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kollender
authors.forename: Josephine
authors.initials: J
authors.lastname: Issakov
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability; D002875:Chromosomes / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009693:Nucleic Acid Hybridization; D011379:Prognosis; D012008:Recurrence; D012306:Risk; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D016615:Telomere / Q000648:ultrastructure*; D016896:Treatment Outcome