Tohoku J. Exp. Med., 2012, 227(2)

Methylation of the CpG Island Near SOX7 Gene Promoter Is Correlated with the Poor Prognosis of Patients with Myelodysplastic Syndrome

RONG FAN,¹ LU-YAO ZHANG,² HONG WANG,³ BO YANG,⁴ TAO HAN,⁴ XIAO-LI ZHAO,¹ WEI WANG,¹ XIAO-QIN WANG¹ and GUO-WEI LIN¹

¹Department of Hematology, Huashan Hospital of Fudan University, Shanghai, P.R. China
²Shanghai Medical College of Fudan University, Shanghai, P.R. China
³Department of Hematology, The First Affiliated Hospital of Soochow University, Shanghai, P.R. China
⁴Fudan-Cinpathogen Clinical& Molecular Research Center, Shanghai, P.R. China

Myelodysplastic syndrome (MDS), characterized by the decreased production of blood cells, often progresses to acute myeloid leukemia (AML), a sign of poor prognosis of MDS. In AML, the Wnt/β-catenin pathway is aberrantly activated, suggesting that the increased pathway activity may be correlated with the development and prognosis of MDS. SOX7 protein, encoded by the sex-determining region Y-box 7 (SOX7) gene, inhibits the activity of the Wnt/β-catenin pathway. Because the DNA methylation can regulate the transcription of SOX7 gene, we used the methylation-specific PCR to investigate the methylation status of the CpG island in MDS patients to determine the potential correlation of the SOX7 methylation with the development and prognosis of MDS. We found that the CpG island of the SOX7 gene was methylated in 58.1% (97/167) of MDS patients, but not in any healthy control. Furthermore, the percentage of patients with the methylated CpG island of the SOX7 gene was significantly higher in patients at advanced stages of MDS than in the patients at early stages. The increased percentages of this SOX7 methylation were also correlated with age, marrow blast levels, and International Prognostic Scoring System (IPSS) risk. After prognostic analysis, we found that patients with the methylated CpG island of the SOX7 gene had shorter overall survival and cumulative survival than patients with unmethylated CpG island. Our findings suggest that the methylation of the CpG island of the SOX7 gene can be used as a predictive factor for the development and prognosis of MDS patients.

keywords —— DNA methylation; myelodysplastic syndromes; prognosis; SOX7; Wnt

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 227, 119-128

Correspondence: Xiao-Qin Wang, Department of Hematology, Huashan Hospital of Fudan University, 12 Wulumuqi Road Central, 200040 Shanghai, P.R. China.

e-mail: wangxiaoqin2010@gmail.com