title: PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines.
abstract: Extensive allelotyping studies have implicated several tumor-suppressor loci on chromosomes 3p, 5q, 6q, 8p, 9pq, 10q, 11q, 14q, 17p, 18q and 19p in human kidney tumorigenesis. The PTEN (also called MMAC1 and TEP1) gene, a candidate tumor suppressor located at chromosome 10q23.3, is mutated in a variety of sporadic malignancies as well as in patients with Cowden disease. To investigate the potential role of the PTEN gene in renal tumorigenesis, we searched for abnormalities of the gene in 68 primary renal-cell carcinomas (RCCs) as well as in 17 renal carcinoma-derived cell lines, using DNA-SSCP, sequencing and microsatellite analysis. Five of 68 (7.5%) primary RCCs exhibited intragenic mutations (3 missense, 1 deletion and 1 splice-site), and 1 of 17 (5.9%) cell lines had an insertion mutation. Loss of heterozygosity of the PTEN gene occurred in 25% of primary RCCs, including the 3 cases with intragenic mutation and the 1 PTEN-mutated cell line. Clinical and histopathological examinations revealed that 4 of the 5 primary tumors with PTEN mutation were high-grade, advanced clear-cell RCCs with distant metastases or renal vein tumor invasions, resulting in poor prognostic courses. The other was a low-stage papillary/chromophilic RCC. Our data suggest that PTEN mutation is observed in a subset of RCCs and that, especially in clear-cell RCCs, it occurs as a late-stage event and may contribute to the invasive and/or metastatic tumor phenotype.
authors.affiliation: Department of Urology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Ota
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: N
authors.initials: N
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Kishida
authors.forename: S
authors.initials: S
authors.lastname: Kawakami
authors.forename: H
authors.initials: H
authors.lastname: Uemura
authors.forename: Y
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatani
authors.forename: M
authors.initials: M
authors.lastname: Hosaka
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human