Genetics of Cowden syndrome: through the looking glass of oncology.

Cowden syndrome (CS) is an autosomal dominant inherited syndrome characterised by hamartoma development in multiple organs and a risk of breast, thyroid and other cancers. The susceptibility gene for this syndrome was mapped to 10q22-23. Subsequently, germline mutations in PTEN, which encodes a dual specificity phosphatase, were found in individuals and families with CS. With the identification of the CS susceptibility gene, DNA-based predictive testing may be offered in theory. Somatic mutations in PTEN have been described in sporadic thyroid tumors, endometrial carcinomas, prostate carcinomas and glioblastoma multiforme. Although initial analyses suggest that the presence of somatic PTEN alterations appear to be associated with more advanced disease in carcinomas of the prostate and brain, this does not appear to be the case in epithelial thyroid tumors.

[1]  J. Barnard,et al.  SMAD4 germline mutations in juvenile polyposis coli. , 1999, Journal of pediatric gastroenterology and nutrition.

[2]  H. Tsou,et al.  Clinical and pathological features of breast disease in Cowden's syndrome: an underrecognized syndrome with an increased risk of breast cancer. , 1998, Human pathology.

[3]  C. Larsson,et al.  Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. , 1997, Cancer research.

[4]  A. Sakurada,et al.  PTEN1 is frequently mutated in primary endometrial carcinomas , 1997, Nature Genetics.

[5]  Kathleen R. Cho,et al.  Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. , 1997, Cancer research.

[6]  J. Boyd,et al.  Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas. , 1997, Cancer research.

[7]  M. Nelen,et al.  Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. , 1997, Human molecular genetics.

[8]  Hong Sun,et al.  TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. , 1997, Cancer research.

[9]  Jing Li,et al.  Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome , 1997, Nature Genetics.

[10]  L. Meisner,et al.  A juvenile polyposis tumor suppressor locus at 10q22 is deleted from nonepithelial cells in the lamina propria. , 1997, Gastroenterology.

[11]  W. K. Alfred Yung,et al.  Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers , 1997, Nature Genetics.

[12]  M. Wigler,et al.  PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer , 1997, Science.

[13]  Darryl Shibata,et al.  Localization of a susceptibility locus for Peutz-Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis , 1997, Nature Genetics.

[14]  B. Neel,et al.  From Form to Function: Signaling by Protein Tyrosine Phosphatases , 1996, Cell.

[15]  D. Lacombe,et al.  Cowden disease. Report of a family and review. , 1996, Annales de genetique.

[16]  S. Mallory.  Cowden syndrome (multiple hamartoma syndrome). , 1995, Dermatologic clinics.

[17]  S. Seal,et al.  Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy? , 1994, Journal of medical genetics.

[18]  Charles B. Wilson,et al.  Association between meningioma and Cowden's disease , 1993, Neurology.

[19]  L. Deftos,et al.  Multiple hamartoma syndrome (Cowden's disease) associated with renal cell carcinoma and primary neuroendocrine carcinoma of the skin (Merkel cell carcinoma). , 1992, American journal of clinical pathology.

[20]  K. Lloyd,et al.  Cowden's disease. A possible new symptom complex with multiple system involvement. , 1963 .