Open Access Highly Accessed Research article

Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

Bekim Sadikovic12, Paul Thorner1, Susan Chilton-MacNeill1, Jeff W Martin4, Nilva K Cervigne3, Jeremy Squire4* and Maria Zielenska12

Author Affiliations

1 Department of Pediatric Laboratory Medicine, Pathology Division, Hospital for Sick Children, Toronto, M5G 1X8 Canada

2 Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, ON, Canada

3 Division of Applied Molecular Oncology, Ontario Cancer Institute, the University Health Network, Toronto, M5G 2M9 Canada

4 Department of Pathology and Molecular Medicine, Richardson Labs, Queen's University, Kingston, K7L 3N6 Canada

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BMC Cancer 2010, 10:202  doi:10.1186/1471-2407-10-202

Published: 13 May 2010

Abstract

Background

Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L.

Methods

Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.

Results

RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders.

Conclusion

These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma.