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MYC Amplification and Polysomy 8 in Chondrosarcoma: Array Comparative Genomic Hybridization, Fluorescent In Situ Hybridization, and Association With Outcome

From the Division of Orthopedic Oncology, Department of Pathology, and Center for Biostatistics, The Arthur James Cancer Hospital and Richard Solove Research Institute, The Ohio State University Medical School; and Columbus Children's Research Institute, Columbus, OH.

Address reprint requests to Carl Morrison, MD, DVM, Director of Pathology Core Facility, 418-M SL, 320 W 10th Ave, Columbus, OH 43210; e-mail: morrison-4{at}medctr.osu.edu

PURPOSE: To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion.

MATERIALS AND METHODS: Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation.

RESULTS: Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance.

CONCLUSION: MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.

Supported by the developmental funds of C.M. as a joint venture of the Department of Pathology and Department of Orthopedic Oncology at The Ohio State University Medical School.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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