Therefore, although some possibly disease associated germline EPHB2 variants do exist and may play a role in colorectal tumor predisposition, the observed EPHB2 inactivation in CRCs is largely due to other mechanisms, such as promoter hypermethylation that has frequently been observed in both MSI and MSS tumors, LOH, and somatic mutations in a coding region repeat sequence in MSI colorectal tumors [6,18]. Here, EPHB2 is linked to colorectal neoplasm.