title: Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies.
abstract: Loss of heterozygosity of chromosome 10q has been reported in approximately 40% of endometrial carcinomas. PTEN, a candidate tumor suppressor gene located at chromosome 10q23.3, was recently identified and found to be homozygously deleted or mutated in several different types of human tumors. To determine if PTEN is a target of 10q loss of heterozygosity in carcinomas of the endometrium, we examined 32 primary endometrial carcinomas for mutations in PTEN. The tumors included the two major histopathological types of endometrial carcinoma: endometrioid (n = 26; 14 microsatellite instability (MI)-positive and 12 MI-negative) and serous (n = 6). Overall, mutations were detected in 50% of the endometrial carcinomas we analyzed. Mutations were present in 12 of 14 (86%) MI-positive and 4 of 12 (33%) MI-negative endometrioid tumors. Furthermore, mutations were found in all three histological grades of MI-positive endometrioid carcinoma. All six serous endometrial carcinomas lacked detectable mutations. To evaluate the role of PTEN in other common malignancies of the female genital tract, 12 serous ovarian carcinomas and 10 squamous cervical carcinomas were analyzed and were negative for mutations. Our results support PTEN as a tumor suppressor gene and suggest that mutations in PTEN play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
authors.forename: H
authors.initials: H
authors.lastname: Tashiro
authors.forename: M S
authors.initials: MS
authors.lastname: Blazes
authors.forename: R
authors.initials: R
authors.lastname: Wu
authors.forename: K R
authors.initials: KR
authors.lastname: Cho
authors.forename: S
authors.initials: S
authors.lastname: Bose
authors.forename: S I
authors.initials: SI
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Parsons
authors.forename: L H
authors.initials: LH
authors.lastname: Ellenson
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D004273:DNA, Neoplasm / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics*; D005091:Exons; D005260:Female; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006579:Heterozygote; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D000070876:Tensins; D025521:Tumor Suppressor Proteins
chemical_list: D004273:DNA, Neoplasm; D008840:Microfilament Proteins; D000070876:Tensins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human