Abstract IA19: Genomic analysis of osteosarcoma: Insights into tumor evolution and therapy response

Abstract

Abstract While significant progress has been made in most other cancers to advance targeted therapy, there has been essentially no change in our approach to treatment of osteosarcoma in over 30 years. Osteosarcomas exhibit an extremely complex genome characterized by multiple copy number changes and structural alterations. Using patient-derived xenografts and primary tumors, we are employing whole-genome sequencing (WGS) and RNAseq to characterize the evolution of this disease with a goal of understanding how evolutionary constraints can identify targetable vulnerabilities. We have identified a number of potential subtypes of osteosarcoma based on copy number alterations and defined how these copy number alterations can be exploited for therapeutic benefit using a large and clinically annotated patient-derived xenograft (PDX) collection. A key current effort is to identify novel genome-informed combination therapies for this disease. To facilitate this work, we have developed a panel of cell lines derived from PDX models, which have also be characterized with regards to their genomic characteristics. We have used these cell lines to screen for response to a wide variety of drugs with the goal of matching response to specific genomic characteristics. Lastly, we are using PDX models to study the process of metastatic progression and have identified a possible role for the enzyme ENPP1 in osteosarcoma metastasis. Citation Format: E. Alejandro Sweet-Cordero. Genomic analysis of osteosarcoma: Insights into tumor evolution and therapy response [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA19.