SFRP4 and malignant colon neoplasm: As mentioned earlier, BRAFV600E-driven colon cancers have increased likelihood of occurring in the proximal colon in the context of increased frequency of DNA methylation-mediated silencing of multiple genes, such as Cdx2, Sfrp4, Cdnk2a, and Sox17. In previous work we have demonstrated that simultaneous inactivation of Cdx2, Sfrp4, Cdnk2a, and Sox17 facilitates BRAFV600E-driven tumor development in organoids derived from proximal colon20.