Analysis of genetic and epigenetic alterations of the PTEN gene in gastric cancer.
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.
Sato
Kiyoshi
K
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Tamura
Gen
G
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Tsuchiya
Takashi
T
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Endoh
Yasushi
Y
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Sakata
Ken
K
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Motoyama
Teiichi
T
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Usuba
Osamu
O
Department of Surgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Kimura
Wataru
W
Department of Surgery, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan, Japan.
Terashima
Masanori
M
Department of Surgery, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan, Japan.
Nishizuka
Satoshi
S
Department of Microbiology and Molecular Genetics, University of California, Irvine College of Medicine, Irvine, CA 92697-4025, USA, USA.
Zou
Tongtong
T
Department of Medicine, Gastroenterology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA, USA.
Meltzer
Stephen J
SJ
Department of Medicine, Gastroenterology Division, University of Maryland School of Medicine, Baltimore, MD 21201, USA, USA.
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
D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human