Cowden syndrome: a critical review of the clinical literature.
ABSTRACT Cowden syndrome (CS) is a multi-system disease involving hamartomatous overgrowth of tissues of all three embryonic origins and increased risks for thyroid, breast and possibly other cancers. Benign breast, thyroid, uterine and skin lesions are also common. Approximately 80% of patients with CS have an identifiable germline mutation in the PTEN gene. The majority of the existing data on the frequencies of component clinical features have been obtained from compilations of case reports in the literature, many of which predate the establishment in 1996 of consensus diagnostic criteria. Many of these reports also suffer from ascertainment bias which emphasized the dermatologic features of the disease. This paper presents an overview of Cowden syndrome focusing on a critical evaluation of the major literature on the component cancers, benign features, and molecular findings in CS, noting the limitations of the published data.
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ABSTRACT: PTEN, a protein tyrosine phosphatase with homology to tensin, is a tumor-suppressor gene on chromosome 10q23. Somatic mutations in PTEN occur in multiple tumors, most markedly glioblastomas. Germ-line mutations in PTEN are responsible for Cowden disease (CD), a rare autosomal dominant multiple-hamartoma syndrome. PTEN was sequenced from constitutional DNA from 25 families. Germ-line PTEN mutations were detected in all of five families with both breast cancer and CD, in one family with juvenile polyposis syndrome, and in one of four families with breast and thyroid tumors. In this last case, signs of CD were subtle and were diagnosed only in the context of mutation analysis. PTEN mutations were not detected in 13 families at high risk of breast and/or ovarian cancer. No PTEN-coding-sequence polymorphisms were detected in 70 independent chromosomes. Seven PTEN germ-line mutations occurred, five nonsense and two missense mutations, in six of nine PTEN exons. The wild-type PTEN allele was lost from renal, uterine, breast, and thyroid tumors from a single patient. Loss of PTEN expression was an early event, reflected in loss of the wild-type allele in DNA from normal tissue adjacent to the breast and thyroid tumors. In RNA from normal tissues from three families, mutant transcripts appeared unstable. Germ-line PTEN mutations predispose to breast cancer in association with CD, although the signs of CD may be subtle.The American Journal of Human Genetics 01/1998; 61(6):1254-60. · 11.20 Impact Factor
- Archives of Dermatology 12/1972; 106(5):682-90. · 4.79 Impact Factor
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ABSTRACT: The tumor suppressor gene PTEN, which is frequently mutated in human cancers, encodes a lipid phosphatase for phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] and antagonizes phosphatidylinositol 3 kinase. Primordial germ cells (PGCs), which are the embryonic precursors of gametes, are the source of testicular teratoma. To elucidate the intracellular signaling mechanisms that underlie germ cell differentiation and proliferation, we have generated mice with a PGC-specific deletion of the Pten gene. Male mice that lacked PTEN exhibited bilateral testicular teratoma, which resulted from impaired mitotic arrest and outgrowth of cells with immature characters. Experiments with PTEN-null PGCs in culture revealed that these cells had greater proliferative capacity and enhanced pluripotent embryonic germ (EG) cell colony formation. PTEN appears to be essential for germ cell differentiation and an important factor in testicular germ cell tumor formation.Development 05/2003; 130(8):1691-700. · 6.21 Impact Factor