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Integrated DNA Copy Number and Expression Profiling Identifies IGF1R as a Prognostic Biomarker in Pediatric Osteosarcoma.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2022 Jul 21; Vol. 23 (14). Date of Electronic Publication: 2022 Jul 21. - Publication Year :
- 2022
-
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.
- Subjects :
- Adolescent
Biomarkers
Child
DNA
DNA Copy Number Variations
Gene Expression Regulation, Neoplastic
Humans
Insulin metabolism
Prognosis
Receptor, IGF Type 1 genetics
Receptor, IGF Type 1 metabolism
Receptors, Growth Factor metabolism
Bone Neoplasms diagnosis
Bone Neoplasms genetics
Bone Neoplasms metabolism
Osteosarcoma diagnosis
Osteosarcoma genetics
Osteosarcoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 23
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35887382
- Full Text :
- https://doi.org/10.3390/ijms23148036