title: PTEN hamartoma tumor syndrome: clinical risk assessment and management protocol.
abstract: The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important phosphatase that counteracts one of the most critical cancer pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathways. Clinically, deregulation of PTEN function resulting in reduced PTEN expression and activity is implicated in human diseases. Cowden syndrome (CS) is an autosomal dominant disorder characterized by benign and malignant tumors. CS-related individual features occur commonly in the general population. Approximately 25% of patients diagnosed with CS have pathogenic germline PTEN mutations, which increase lifetime risks of breast, thyroid, uterine, renal and other cancers. PTEN testing and intensive cancer surveillance allow for early detection and treatment of these cancers for mutation positive patients and their relatives. In this review, we highlight our current knowledge of germline PTEN mutations in relation to human disease. We review current clinical diagnosis and management recommendations for PHTS including recent discoveries in understanding PTEN function regulation and how this can be exploited therapeutically.
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Division of Medical Oncology, National Cancer Centre, Singapore 169610, Singapore; Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore 169610, Singapore.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
authors.affiliation: Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA; CASE Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: engc@ccf.org.
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D000818:Animals; D019468:Disease Management; D020022:Genetic Predisposition to Disease / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006223:Hamartoma Syndrome, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D018570:Risk Assessment; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Cancer; PI3K/AKT signaling; PTEN hamartoma tumor syndrome; Tumor suppressor