title: Analysis of genetic and epigenetic alterations of the PTEN gene in gastric cancer.
abstract: The PTEN tumor suppressor gene on 10q23.3, responsible for the Cowden and Bannayan-Zonana syndromes, encodes a dual-specificity phosphatase able to dephosphorylate both tyrosine phosphate and serine/threonine phosphate residues. Mutational inactivation of PTEN has been reported in various malignancies, including endometrial cancers, ovarian cancers, and glioblastomas. In this study, we investigated PTEN gene mutations in 10 gastric cancer cell lines and 58 primary gastric cancers by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP). Hypermethylation of promoter region CpG islands, an alternative mechanism of gene inactivation to coding region mutations, was also evaluated by methylation specific PCR (MSP). Only one (1.7%) of the 58 primary tumors carried a somatic 5-bp deletion in intron 7 of PTEN, which did not alter the mRNA sequence, and no mutations were detected in any of the cell lines. Similar levels of PTEN mRNA expression were observed in all cell lines and primary tumors studied by RT-PCR, and PTEN promoter CpG islands remained unmethylated. Therefore, we conclude that PTEN does not participate in gastric carcinogenesis as a tumor suppressor gene.
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Endoh
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sakata
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
authors.affiliation: Department of Surgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Usuba
authors.affiliation: Department of Surgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kimura
authors.affiliation: Department of Surgery, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine College of Medicine, Irvine, CA 92697-4025, USA, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishizuka
authors.affiliation: Department of Medicine, Gastroenterology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA, USA.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Zou
authors.affiliation: Department of Medicine, Gastroenterology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human