期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 14, 页码 -出版社
MDPI
DOI: 10.3390/ijms23148036
关键词
osteosarcoma; bone; pediatric; cancer; treatment; biomarker; metastasis; prognosis
资金
- NCI [U01 CA114757-04]
This study revealed the heterogeneity of osteosarcoma in younger populations and identified several genes, such as IGF1R and FGFR2, that are associated with the pathogenesis of the disease. These genes were found to have a significant impact on the prognosis of patients.
Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a receptor tyrosine kinase which binds IGF1 and IGF2 to activate downstream pathways involved in cell apoptosis and proliferation. We identify prevalent amplification of IGF1R corresponding with increased gene expression in patients with poor survival outcomes. Our results substantiate previously tenuously associated copy number abnormalities identified in smaller datasets (13q34+, 20p13+, 4q35-, 20q13.33-), and indicate the significance of high fibroblast growth factor receptor 2 (FGFR2) expression in distinguishing patients with poor prognosis. FGFR2 is involved in cellular proliferation processes such as division, growth and angiogenesis. In summary, our findings demonstrate the prognostic significance of several genes associated with osteosarcoma pathogenesis.
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