Integrated DNA Copy Number and Expression Profiling Identifies IGF1R as a Prognostic Biomarker in Pediatric Osteosarcoma

Authors

Aaron M Taylor
Jiayi M Sun
Alexander Yu
Horatiu Voicu
Jianhe Shen
Donald A Barkauskas
Timothy J Triche
Julie M Gastier-Foster
Tsz-Kwong Man
Ching C Lau

Publication Date

7-21-2022

Journal

International Journal of Molecular Sciences

DOI

10.3390/ijms23148036

PMID

35887382

PMCID

PMC9319262

PubMedCentral® Posted Date

7-21-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adolescent, Biomarkers, Bone Neoplasms, Child, DNA, DNA Copy Number Variations, Gene Expression Regulation, Neoplastic, Humans, Insulin, Osteosarcoma, Prognosis, Receptor, IGF Type 1, Receptors, Growth Factor, osteosarcoma, bone, pediatric, cancer, treatment, biomarker, metastasis, prognosis

Abstract

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.