Short telomeres: a novel potential predictor of relapse in Ewing sarcoma.
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.
Avigad
Smadar
S
Molecular Oncology, Felsenstein Medical Research Center, Petach Tikva, Israel. savigad@post.tau.ac.il
Naumov
Inna
I
Ohali
Anat
A
Jeison
Marta
M
Berco
Gili Halevy
GH
Mardoukh
Jacques
J
Stark
Batia
B
Ash
Shifra
S
Cohen
Ian J
IJ
Meller
Isaac
I
Kollender
Yehuda
Y
Issakov
Josephine
J
Yaniv
Isaac
I
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