title: Somatic mutations of the PTEN tumor suppressor gene in sporadic follicular thyroid tumors.
abstract: The PTEN (MMAC1/TEP1) tumor suppressor gene was recently isolated and mapped to human chromosome band 10q23. Homozygous deletions and mutations of PTEN were observed in cell lines and sporadic cancers of the breast, kidney, and central nervous system. Germline mutations in PTEN were recently found in Cowden disease, an autosomal dominant inherited syndrome, previously mapped to chromosome bands 10q22-23. This disease is associated with a wide variety of malignancies and hamartomas of ectodermal, mesodermal, and endodermal origin. The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype). To determine the involvement of PTEN in sporadic follicular thyroid tumors, we first analyzed sporadic follicular adenomas and carcinomas for deletions of the PTEN gene. Loss of heterozygosity was found in 7/26 (27%) follicular carcinomas and 2/27 (7%) follicular adenomas, one of which was a small hemizygous deletion (approximately 3 cm). Sequence analysis of the entire PTEN coding region revealed two mutations in carcinomas with 10q loss. Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors.
authors.affiliation: Head and Neck Cancer Research, Department of Otolaryngology, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
authors.forename: N
authors.initials: N
authors.lastname: Halachmi
authors.forename: S
authors.initials: S
authors.lastname: Halachmi
authors.forename: E
authors.initials: E
authors.lastname: Evron
authors.forename: P
authors.initials: P
authors.lastname: Cairns
authors.forename: K
authors.initials: K
authors.lastname: Okami
authors.forename: M
authors.initials: M
authors.lastname: Saji
authors.forename: W H
authors.initials: WH
authors.lastname: Westra
authors.forename: M A
authors.initials: MA
authors.lastname: Zeiger
authors.forename: J
authors.initials: J
authors.lastname: Jen
authors.forename: D
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000236:Adenoma / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human