860

RUNX2

AML3|CBFA1|CCD|CCD1|OSF-2|OSF2|PEA2aA|PEBP2A1|PEBP2A2|PEBP2aA|PEBP2aA1;runt-related transcription factor 2;RUNX2;runt-related transcription factor 2

CBF-alpha-1|PEA2-alpha A|PEBP2-alpha A|SL3-3 enhancer factor 1 alpha A subunit|SL3/AKV core-binding factor alpha A subunit|acute myeloid leukemia 3 protein|core-binding factor, runt domain, alpha subunit 1|oncogene AML-3|osteoblast-specific transcription

6p21

protein-coding

BACKGROUND: Human osteosarcoma is the most common pediatric bone tumor. There islimited 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 ofexpression relative to normal osteoblasts. In addition to being overexpressed inosteosarcoma 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.