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

BMC Cancer

Research Article

Jeremy Squire¹  Jeff W Martin¹  Paul Thorner²  Susan Chilton-MacNeill²  Bekim Sadikovic³  Maria Zielenska³  Nilva K Cervigne⁴ 

[1] Department of Pathology and Molecular Medicine, Richardson Labs, Queen's University, K7L 3N6, Kingston, Canada;Department of Pediatric Laboratory Medicine, Pathology Division, Hospital for Sick Children, M5G 1X8, Toronto, Canada;Department of Pediatric Laboratory Medicine, Pathology Division, Hospital for Sick Children, M5G 1X8, Toronto, Canada;Genetics and Genome Biology Program, Hospital for Sick Children, Toronto, ON, Canada;Division of Applied Molecular Oncology, Ontario Cancer Institute, the University Health Network, M5G 2M9, Toronto, Canada;

关键词: Osteosarcoma;    Osteosarcoma Cell Line;    RUNX2 Expression;    Copy Number Loss;    Gene Expression Network;   

DOI  :  10.1186/1471-2407-10-202

 received in 2009-10-29, accepted in 2010-05-13,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundHuman 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.MethodsOur 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.ResultsRECQL4, 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.ConclusionThese 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.

【 授权许可】

Unknown   
© Sadikovic et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.