High frequency of genomic instability in Ewing family of tumors.
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.
Ohali
Anat
A
Molecular Oncology, Felsenstein Medical Research Center, Rabin Medical Campus, Sackler Faculty of Medicine, Tel Aviv University, 39 Jabotinski St, Petah Tikva 49100, Israel.
Avigad
Smadar
S
Cohen
Ian J
IJ
Meller
Isaac
I
Kollender
Yehuda
Y
Issakov
Josephine
J
Goshen
Yacov
Y
Yaniv
Isaac
I
Zaizov
Rina
R
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
D004273:DNA, Neoplasm