Pei Liu1,2, Cassandra Garbutt1, Francis J Hornicek1, Fuyun Liu3, Zhenfeng Duan4. 1. Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, U.S.A. 2. Department of Orthopaedics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China. 3. Department of Orthopaedics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China liufuyun111@126.com zduan@mgh.harvard.edu. 4. Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, U.S.A. liufuyun111@126.com zduan@mgh.harvard.edu.
Abstract
BACKGROUND: p73 is a tumor-suppressor gene with significant homology to p53. Abnormal promoter methylation of p73 is present in different types of cancer. However, the promoter methylation status of p73 in chondrosarcoma (CS) is unknown. MATERIALS AND METHODS: p73 promoter methylation status was evaluated by quantitative polymerase chain reaction (PCR), p73 protein expression by western blot, and the relationship between p73 methylation and clinical data was analyzed. RESULTS: In 42 tumor tissues with CS, we found that three cases (7%) maintained methylation levels between 51% and 75%, and 39 cases (93%) had levels between 76% and 100%. p73 methylation level was significantly (p<0.05) positively associated with histological grade. Loss of p73 protein expression was correlated with high methylation of the p73 promoter; p73 expression was restored after exposure to a demethylating drug. CONCLUSION: p73 is epigenetically silenced in CS due to promoter methylation, which suggests the utility of p73 methylation as a biomarker. Copyright
BACKGROUND:p73 is a tumor-suppressor gene with significant homology to p53. Abnormal promoter methylation of p73 is present in different types of cancer. However, the promoter methylation status of p73 in chondrosarcoma (CS) is unknown. MATERIALS AND METHODS:p73 promoter methylation status was evaluated by quantitative polymerase chain reaction (PCR), p73 protein expression by western blot, and the relationship between p73 methylation and clinical data was analyzed. RESULTS: In 42 tumor tissues with CS, we found that three cases (7%) maintained methylation levels between 51% and 75%, and 39 cases (93%) had levels between 76% and 100%. p73 methylation level was significantly (p<0.05) positively associated with histological grade. Loss of p73 protein expression was correlated with high methylation of the p73 promoter; p73 expression was restored after exposure to a demethylating drug. CONCLUSION:p73 is epigenetically silenced in CS due to promoter methylation, which suggests the utility of p73 methylation as a biomarker. Copyright