The highly frequent methylation of SFRP1, HIC1 and PTEN could lead to an increase in proliferation, inhibition of apoptosis and promotion of survival advantage in CCA through increased Wnt/β-catenin signal transduction through the impaired p53-responsive pathway and activated PI3K and its downstream effectors as previously reported in other cancers (Wales et al, 1995; Finch et al, 1997; Melkonyan et al, 1997; Besson et al, 1999; Nicoll et al, 2001; Sulis and Parsons, 2003; Chen et al, 2005; Manning and Cantley, 2007; Takagi et al, 2008; Fleuriel et al, 2009). The gene discussed is PTEN; the disease is cholangiocarcinoma.