期刊
CANCER GENETICS
卷 205, 期 7-8, 页码 391-404出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cancergen.2012.05.012
关键词
Ewing sarcoma; copy number; outcome; SMARCB1/INI1/SNF5; CEBPB
资金
- St. Baldrick's Foundation
- Sarcoma Alliance for Research through Collaboration (SARC) Career Development Award
- Damon Runyon Clinical Investigator Award
- Eunice Kennedy Shriver Children's Health Research Career Development [NICHD 5K12HD001410]
- NIH [R21 CA138295, R01 CA140394, P30 CA042014]
- Terri Anna Perine Sarcoma Fund
- University of Utah Department of Pediatrics and Huntsman Cancer Institute/Huntsman Cancer Foundation
- Children's Oncology Group (COG)
Ewing sarcoma (ES) is the second most common bone tumor in children and young adults, with dismal outcomes for metastatic and relapsed disease. To better understand the molecular pathogenesis of ES and to identify new prognostic markers, we used molecular inversion probes (MIPs) to evaluate copy number alterations (CNAs) and loss of heterozygosity (LOH) in formalin-fixed paraffin-embedded (FFPE) samples, which included 40 ES primary tumors and 12 ES metastatic lesions. CNAs were correlated with clinical features and outcome, and validated by immunohistochemistry (IHC). We identified previously reported CNAs, in addition to SMARCB1 (INI1/SNF5) homozygous loss and copy neutral LOH. IHC confirmed SMARCB1 protein loss in 7-10% of clinically diagnosed ES tumors in three separate cohorts (University of Utah [N = 40], Children's Oncology Group [N = 31], and University of Michigan [N = 55]). A multifactor copy number (MCN)-index was highly predictive of overall survival (39% vs. 100%, P < 0.001). We also identified RELN gene deletions unique to 25% of ES metastatic samples. In summary, we identified both known and novel CNAs using MIP technology for the first time in FFPE samples from patients with ES. CNAs detected by microarray correlate with outcome and may be useful for risk stratification in future clinical trials.
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