E-Cadherin, Hereditary Diffuse Gastric Cancer
HDGC; Hereditary diffuse gastric carcinoma
E-cadherin gastric carcinoma or hereditary diffuse gastric carcinoma (HDGC) is a form of gastric cancer in patients with germline alterations in the CDH1 gene. HDGC is an autosomal-dominant cancer-susceptibility syndrome and is characterized by diffuse gastric cancer and lobular breast cancer. In 1998, Guildford et al. identified germline mutations in the CDH1 gene to be the cause of HDGC by linkage analysis and mutation screening in three Maori kindreds with multigenerational gastric cancer in New Zealand.
CDH1 encodes the protein E-cadherin, which plays an important role in cell polarity and the maintenance of epithelial integrity. Due to mutations in CDH1, the cell-cell adhesion mediated by E-cadherin is lost, which causes disruption of the correct spatial organization of the cells. This interferes with processes that regulate cell division, such as the orientation of the mitotic spindle. Abrogated cell polarity may...
References and Further Reading
- Carneiro, F., Huntsman, D. G., Smyrk, T. C., Owen, D. A., Seruca, R., Pharoah, P., et al. (2004). Model of the early development of diffuse gastric cancer in E-cadherin mutation carriers and its implications for patient screening. The Journal of Pathology, 203(2), 681–687.CrossRefPubMedGoogle Scholar
- Hansford, S., Kaurah, P., Li-Chang, H., et al. (2015). Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond. JAMA Oncology.Google Scholar
- van der Post, R. S., Vogelaar, I. P., Carneiro, F., et al. (2015). Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers. Journal of medical genetics. 52(6), 361–374.Google Scholar