Using next-generation sequencing technology for extensive mutation analysis and bead-array technology for genome-wide DNA methylation analysis on the same tumor samples [9], ESCCs were recently characterized and WNT pathway was reported to be a key altered pathway in ESCC, activated potentially by aberrant methylation of its negative regulators, such as SFRP1, SFRP2, SFRP4, SFRP5, SOX17, and WIF1 (33%). Here, SFRP4 is linked to esophageal squamous cell carcinoma.