title: High frequency of genomic instability in Ewing family of tumors.
abstract: We tested Ewing sarcoma tumors for microsatellite instability (MSI) and loss of heterozygosity (LOH) to investigate the role of genomic instability (GI) in this sarcoma. We detected a high frequency of GI (57%), mostly on 1p and 11p, 35% and 30%, respectively. Patients with GI compared to those with stable genome had a median progression-free survival (PFS) and overall survival (OS) of 24 months and 70 months, compared with 39 and 84 months, respectively. MSI was observed in 48% (11/23) of the tumor samples. Low-MSI (L-MSI) patients (with MSI presented at only one locus) tended to have a better prognosis, 70% PFS, compared with 25% in the high-MSI (H-MSI) group (P=0.13). LOH without MSI did not correlate with progression. H-GI (MSI and/or LOH in > or =30% of tested markers) tended to associate with an adverse prognosis (P=0.28), and correlated significantly with the pelvic site of the primary tumor (P=0.02). The instability of 1p was not associated with progression, while alterations at the 11p locus tended to correlate with a more aggressive disease (P=0.18). Our data suggest that GI may play a role in Ewing sarcoma clinical behavior and outcome.
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Rabin Medical Campus, Sackler Faculty of Medicine, Tel Aviv University, 39 Jabotinski St, Petah Tikva 49100, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Ohali
authors.forename: Smadar
authors.initials: S
authors.lastname: Avigad
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: Yacov
authors.initials: Y
authors.lastname: Goshen
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Rina
authors.initials: R
authors.lastname: Zaizov
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D042822:Genomic Instability; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D011379:Prognosis; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm