CDH1 on 16q22.1 encodes E-cadherin which functions in intercellular adhesion. E-cadherin is involved in transmitting chemical signals and controlling cell maturation and movement, and acts as a tumor suppressor. A lack of functional E-cadherin impairs cell adhesion and increases the likelihood of invasion and metastasis of tumor cells. CDH1 is altered by mutation or deletion in various cancers and loss of E-cadherin has been demonstrated in a variety of sporadic cancer types including breast cancer, gastric cancer, colorectal cancer, and esophageal cancer. Along with point mutations and loss of heterozygosity (LOH), epigenetic silencing by hypermethylation of the CDH1 promoter has been associated with the loss of E-cadherin gene expression during cancer progression. Individuals with a germline CDH1 mutation have an increased risk of developing diffuse gastric cancer and breast cancer. More than 100 different pathogenic germline mutations are distributed throughout the CDH1 gene including splice-site sequences and have been found to cause a familial cancer disorder called hereditary diffuse gastric cancer (HDGC). Somatic CDH1 alterations are also found in approximately 30% of all patients with gastric cancers, both diffuse and intestinal types. Genetic alterations of CDH1 have been identified in 4% of colorectal adenocarcinomas. CDH1 D400V lies within the Cadherin domain 3 of the Cdh1 protein (UniProt.org). D400V has not been characterized in the scientific literature and therefore, its effect on CDH1 protein function is unknown.
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