Genetic imbalances revealed by comparative genomic hybridization in Ewing tumors.
Ewing tumors are characterized by reciprocal translocations involving the EWS gene on 22q12 fused to ETS transcription-factor family members. Little is known about further aberrations contributing to tumor development and progression. Sixty-two frozen tumors with known EWS rearrangements (52 primary tumors, 10 relapses) of ET patients registered in the EICESS protocol were analyzed by comparative genomic hybridization (CGH). The median number of changes in 52 primary and 10 relapsed cases was 2.5 and 5.0 per tumor (P = 0.153). Frequent abnormalities included gains of chromosomes 8, 12, 20, and 1q and losses of 16q and 19q. Neither number nor type of aberration was associated with histology, tumor size, disease stage, tumor localization, or histologic tumor response to chemotherapy. Among the 52 primary tumors, 26 with Type I fusion (EWS exon 7 to FLI1 exon 6) and 26 with other fusion types had a median of 2.0 and 3.0 aberrations per tumor, respectively (P = 0.031). Combinations of gains of chromosomes 8 and 12, gains of chromosome 20, and either gains of 8q or 18q and losses of 16q and 17p frequently occurred. The cumulative overall survival (OAS) was different between 35 patients with <5 aberrations and 13 patients with > or =5 aberrations (P = 0.009). Univariate analysis showed that patients with gains of 1q, 2q, 12, and 20 or losses of 16q and 17p had significantly lower OAS than those without aberrations. By multivariate analysis, loss of 16q (relative risk [RR] = 5.3; P = 0.0006) was an independent prognostic factor.
Ozaki
T
T
Department of Orthopaedics, Westfälische Wilhelms-University, Domagkstrasse 17, 48149 Münster, Germany.
Paulussen
M
M
Poremba
C
C
Brinkschmidt
C
C
Rerin
J
J
Ahrens
S
S
Hoffmann
C
C
Hillmann
A
A
Wai
D
D
Schaefer
K L
KL
Boecker
W
W
Juergens
H
H
Winkelmann
W
W
Dockhorn-Dworniczak
B
B
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations / Q000235:genetics; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods*; D012512:Sarcoma, Ewing / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D012737:Sex Factors; D014178:Translocation, Genetic / Q000235:genetics