Frequent methylation-mediated silencing of extracellular (SFRPs and DKKs) [20]–[22] and cytosolic (APC, AXIN2 and DACT3) [23]–[25] WNT antagonists, nuclear proteins (SOX7 and SOX17) [26], [27], and non-transforming WNT families (WNT5A, WNT7A and WNT9A) occurs in cancers [28]–[30], indicating that the epigenetic inactivation of WNT-signaling negative regulators plays a critical role in tumor pathogenesis. This evidence concerns the gene AXIN2 and cancer.