Osteosarcoma is an aggressive cancer of bone, which typically occurs during adolescence. The genetic hallmark of osteosarcoma is the presence of extensive and complex genomic rearrangements. However, few consistent aberrations have been identified, hampering the development of targeted therapy for osteosarcoma. Next generation RNA-sequencing (RNA-seq) is a powerful tool for comprehensive characterization of whole transcriptome, with the unique ability of identifying novel fusion genes. We applied paired-end RNA-seq to explore the transcriptome of 16 human OS cell lines and primary osteoblasts from two healthy individuals. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for each sample. Several thousand SNVs (single nucleotide variants) that have not been reported in the dbSNP database were identified. Bioinformatic analysis identified several fusion genes (e.g. PAFAH1B2-FOXR1and FAM119B-TSFM), which involved both known cancer related genes as well as genes previously unrelated to cancer. Fusion transcripts were validated using RT-PCR, Western blot and capillary sequencing. These rearrangements tended to occur at copy number transitions on the partner chromosome regions. Our findings have the potential to provide important insights into osteosarcoma biology, and potential translational applications for diagnostic and therapeutic development.

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 5070. doi:1538-7445.AM2012-5070