CDH1 and Familial gastric cancer: But when it is a due to the E-cadherin dysfunction in the cells, which helps in cellular binding, the cells become non-cohesive and the tissue loses its basic structure resulting in metastasis and unregulated growth of the cells [31]. As in HDGC, the second-hit resulting in the tumor growth is most commonly due to promoter methylation with one case series showing that in 77% of their study population, the main cause of inactivation of the tumor suppressor gene CDH1 was promoter methylation [32].