title: Mutations in PI3K/AKT pathway genes and amplifications of PIK3CA are associated with patterns of recurrence in gastric cancers.
abstract: Mutations in genes involved in the PI3K/AKT pathway and amplifications of the PIK3CA gene in gastric cancer and their associations with clinicopathological characteristics and EBV infection were analyzed in this study. A total of 431 patients with gastric adenocarcinomas were enrolled, and 39 mutation hotspots were evaluated in these patients using MALDI-TOF mass spectrometry were analyzed. PIK3CA amplifications were analyzed using real-time quantitative PCR. Regarding patients with intestinal-type gastric cancer, those with mutations in PI3K/AKT pathway genes were also more likely to have tumors located in the lower-third of the stomach than were those without mutations. Regarding patients with diffuse-type gastric cancer, those with PI3K/AKT pathway mutations were more likely to have tumors located in the upper-third of the stomach and to have more hematogenous metastases, particularly in the liver and lungs, than were patients without such mutations (22.2% vs. 4.5%). No significant survival difference was observed between patients with vs. without PI3K/AKT pathway mutations. Mutations in PI3K/AKT pathway genes were associated with hematogenous metastasis in patients with diffuse-type gastric cancer. Only when the tumors were located in the middle-third of stomach, tumor with mutations of the PIK3CA gene or mutations of the PI3K/AKT pathway genes were associated with more EBV infection than those without mutations. Patients with PIK3CA amplifications were more likely to have diffuse-type and poorly differentiated gastric cancers and were more likely to experience peritoneal recurrence compared with those without PIK3CA amplifications. Even upon subgroup analysis, PI3KCA amplifications were found to not affect the patients' outcomes.
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Fang
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Kuo-Hung
authors.initials: KH
authors.lastname: Huang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Yuan-Tzu
authors.initials: YT
authors.lastname: Lan
authors.affiliation: Genome Research Center, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Shih-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.|Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|National Yang-Ming University Hospital, Yilan City, Taiwan.
authors.forename: Su-Shun
authors.initials: SS
authors.lastname: Lo
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan.
authors.forename: Anna Fen-Yau
authors.initials: AF
authors.lastname: Li
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Chew-Wun
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei City, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei City, Taiwan.|Institute of Pharmacology, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan.|School of Medicine, National Yang-Ming University, Taipei City, Taiwan.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shyr
mesh_terms: D000368:Aged; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3K/AKT pathway; PIK3CA amplifications; diffuse-type; prognosis; recurrence pattern