CDH1

About CDH1

CDH1 on chromosome 16q22.1 encodes E cadherin, a calcium dependent cell to cell adhesion molecule that forms adherens junctions between epithelial cells and links to the actin cytoskeleton through catenins. Germline CDH1 variants cause hereditary diffuse gastric cancer, an autosomal dominant syndrome with a high lifetime risk of diffuse type gastric cancer, composed of signet ring cells, and an increased risk of lobular breast cancer. The syndrome was first described in 1998 in Maori families in New Zealand. Diffuse gastric cancer spreads beneath the stomach lining rather than forming a visible mass, which makes it difficult to detect by endoscopy, and risk reducing total gastrectomy is one of the options discussed with carriers, alongside endoscopic surveillance. Some CDH1 variants are also associated with cleft lip and palate. Somatic CDH1 inactivation is a hallmark of sporadic diffuse gastric cancers and lobular breast cancers, the loss of E cadherin explaining the characteristic single file growth pattern of lobular carcinoma. Loss of E cadherin also disrupts epithelial integrity and is a central feature of the epithelial to mesenchymal transition, in which cells gain migratory and invasive properties, and the switch from E cadherin to N cadherin is associated with cancer progression.