A CpG site in the promoter region of frizzled related protein (FRZB), a modulator of WNT signaling known to be involved in regulation of bone development, was hypermethylated in metastatic cSCC compared to non-metastatic primary cSCC (median methylation: 46.7% vs. 4.7%) [48]. The gene discussed is FRZB; the disease is skin squamous cell carcinoma.