Abstract 68: Comparative transcriptome analysis of primary tumor and matched tumor thrombus reveals that coagulation cascades activation contributes to the venous metastases of osteosarcoma

Abstract

Abstract Comparative transcriptome analysis of primary tumor and matched tumor thrombus reveals that coagulation cascades activation contributes to the venous metastases of osteosarcoma Osteosarcoma is the most frequent malignant primary tumor of bone in children and adolescents with an approximately 5-year survival about 50-60%. Lung metastasis remains as the most challenging condition during treatment and follow-up, which has been regarded as the main reason for bottle neck of prognosis. Tumor thrombus is occasionally diagnosed in patients with malignant tumor. It usually exists during tumor angiogenesis associated with proliferation and metastasis. The presentation shows aggressive features and advanced stage of the disease. Tumor thrombus is associated with highly metastasis potential. Based on the evolution theory of tumor metastasis, tumor thrombus can be the intermediate phase between local invasion and distal metastasis. In order to investigate the underlying mechanism and identify candidate metastasis driver genes, we collected a set of high quality paired tumor tissue, both the primary site and corresponding tumor thrombus that were treated by thrombectomy. In this study, we present a large-scale transcriptome analysis, by RNA sequencing, of 4 patients diagnosed with large pelvic osteosarcoma with tumor thrombus. The dysregulated genes between primary site and thrombus suggested that the complement and coagulation cascades, focal adhesion and extracellular matrix receptor was correlated with the formation of tumor thrombus. Tissue factor was identified as a major marker in coagulation pathway activation. We also identified NOTCH2NL-NBPF1 fusion genes in all four patients. All of these findings broaden our knowledge of osteosarcoma thrombus and may also contribute to the novel mechanism of metastasis in osteosarcoma. Citation Format: Tao Ji, Yifei Wang, Yi Guo, Dasen Li, Haijie Liang, Tingting Ren, Wei Guo. Comparative transcriptome analysis of primary tumor and matched tumor thrombus reveals that coagulation cascades activation contributes to the venous metastases of osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 68.