Abstract 5579: Genomic approach to the prediction of chemotherapeutic sensitivity in osteosarcoma

Abstract

Abstract PURPOSE: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Despite of recent progress of combined therapy, about 30% of OS patients die because of tumor progression or relapse. It is generally accepted that sensitivity of neoadjuvant chemotherapy is the most important prognostic factor for OS, however, there have been few analyses documenting molecular markers that predicts the chemosensitivity of OS patients. The aim of this study is to identify possible genomic biomarkers for the prediction of chemosensitivity and prognosis for OS patients. METHODS: Pretherapeutic biopsy samples of 22 pediatric OS patients treated in Chiba cancer center who had homogeneous clinicopathological- and therapeutic- background were analyzed. In our study, patients were divided into 3 groups; group A includes 8 patients who demonstrated a good response for 1st regimen, group B includes 6 patients who were resistant to 1st regimen but showed good response to 2nd regimen, group C includes 8 patients who did not respond to neither 1st nor 2nd regimen. Genomic DNAs were prepared from each frozen tissue and used for aCGH analysis with Agilent 44k DNA microarray. RESULTS: According to the results of comparative analysis of CNV patterns in each patient, three chromosomal patterns strongly separated group A from B&C or C from A&B were identified. Gain of 5p12 was found in 7 out of 8 patients of group A, while only 1 out of 14 patients of group B and C (sensitivity 87.5%, specificity 92.9%). On the other hand, loss of 9q21 and amplification of 12q14 were specifically observed in group C, but not in A and B (sensitivity 100%, specificity 92.9%). The average of copy numbers within the region of 5p12 and 9q21.3 on each patient were calculated, and 2-dimensional plot of these two values clearly showed that each group formed distinct clusters. CONCLUSION: Our results indicated that copy number changes in OS biopsy samples could be good markers to determine suitable chemotherapeutic regimen for individual patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5579. doi:1538-7445.AM2012-5579