title: Screening for germline phosphatase and tensin homolog-mutations in suspected Cowden syndrome and Cowden syndrome-like families among uterine cancer patients.
abstract: Cowden syndrome (CS) is an autosomal dominant disorder characterized by multiple hamartomas in the breast, thyroid and endometrium, with a prevalence of 1 per 250,000. Females with CS have a 21-28% lifetime risk of developing uterine cancer. Germline mutations in the phosphatase and tensin homolog (PTEN) gene, a tumor suppressor gene, are responsible for 30-80% of CS cases.PTENis a nine-exon gene, located on chromosome 10q23.3, which encodes the 403 amino acid PTEN protein. It negatively regulates the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting various cellular processes and signaling pathways. The present study examined whetherPTENmutations are present in CS-like families with uterine cancer (UC). UC patients underwent surgery at Karolinska University Hospital, Stockholm, Sweden (2008-2012). Pedigrees were analyzed and 54 unrelated CS-like families were identified. CS-like families were defined as having at least one occurrence of uterine cancer and one of breast cancer, as well as at least one additional Cowden-associated tumor (uterine, breast, thyroid, colon or kidney cancer) in the same individual or in first-degree relatives. Genomic DNA was amplified using polymerase chain reaction, and DNA sequencing analysis of all nine exons of thePTENgene was conducted. No germlinePTENmutations or polymorphisms were identified. GermlinePTENmutations are rare in CS-like families with uterine cancer, therefore, genetic screening must be restricted to patients that meet the strict National Comprehensive Cancer Network criteria. Gynecologists must be aware of the CS criteria and identify potential cases of CS in females where uterine cancer is the sentinel cancer.
authors: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, The Karolinska Institute, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden ; Division of Obstetrics and Gynecology, Karolinska University Hospital, Huddinge, Stockholm 141 86, Sweden.
authors: Gerasimos
authors: G
authors: Tzortzatos
authors: Department of Clinical Genetics, Akademiska Hospital, Uppsala University, Uppsala 751 85, Sweden.
authors: Christos
authors: C
authors: Aravidis
authors: Department of Clinical Genetics, The Karolinska Institute, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden ; Department of Molecular Medicine and Surgery, The Karolinska Institute, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden.
authors: Annika
authors: A
authors: Lindblom
authors: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, The Karolinska Institute, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden.
authors: Miriam
authors: M
authors: Mints
authors: Department of Clinical Genetics, The Karolinska Institute, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden ; Department of Molecular Medicine and Surgery, The Karolinska Institute, Karolinska University Hospital, Solna, Stockholm 171 76, Sweden.
authors: Emma
authors: E
authors: Tham
keywords: Cowden syndrome-like families; germline phosphatase and tensin homolog mutations; uterine cancer