EN1 and cancer: RASSF1A is hypermethylated in almost every cancer type and was the first TSG shown to be specifically methylated in the placenta. Methylation of multiple negative regulators of Wnt signaling (APC, WIF-1, SFRP2, EN1) demonstrates coordinated epigenetic regulation of signaling pathways in placenta and cancer. Multiple examples of monoallelic methylation indicate a potential suite of novel imprinted genes involved in the regulation of placentation in humans.