TY - CHAP M1 - Book, Section TI - Cowden Syndrome A1 - Eng, Charis A1 - Parsons, Ramon A2 - Valle, David L. A2 - Antonarakis, Stylianos A2 - Ballabio, Andrea A2 - Beaudet, Arthur L. A2 - Mitchell, Grant A. PY - 2019 T2 - The Online Metabolic and Molecular Bases of Inherited Disease AB - Cowden syndrome (CS) is an autosomal dominant disorder characterized by multiple hamartomas and a risk of breast and thyroid cancers.The great majority of tumors, including those of the thyroid and breast, are benign. Up to 10 percent of affected individuals develop nonmedullary thyroid carcinoma, and up to 50 percent of affected females develop breast cancer.The pathognomonic hamartoma is the trichilemmoma, a benign tumor of the infundibulum of the hair follicle.The susceptibility gene for CS is a tumor-suppressor gene as evidenced by loss of heterozygosity in the PTEN region of 10q23 in various tumors and by transfection.The CS gene PTEN was isolated by a combination of genetic mapping analyses, somatic genetics, and a candidate gene approach. PTEN, located on 10q23.3, encodes a 403-amino acid protein, which contains a phosphatase signature motif and has sequences homologous to tensin.PTEN is a dual-specificity lipid phosphatase. PTEN is the 3-phosphatase for phosphotidylinositol-3,4,5-triphosphate and, hence, coordinately regulates the cell survival factor PKB/Akt via the PI3 kinase signaling pathway.Germ line mutations in PTEN have been found in CS families as well as in the related but distinct hamartoma disorder Bannayan-Ruvalcaba-Riley syndrome. These mutations result in predicted protein truncation or likely loss of function, hence supporting its predicted function as a tumor suppressor.Somatic mutations of PTEN occur in a broad spectrum of sporadic tumors, which is almost always biallelic. However, alternate mechanisms of PTEN inactivation do occur. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - ommbid.mhmedical.com/content.aspx?aid=1181416126 ER -