title: Occurrence of low frequency PIK3CA and AKT2 mutations in gastric cancer.
abstract: The PI3K/AKT signal transduction pathway has distinct functional roles in tumor progression. PIK3CA was reported to harbor the hot-spot in many types of tumor. Akt, the downstream of PI3K, its family members especially AKT2 activation in human cancer has been extensively studied, but its activation by mutation was less reported. The occurrence of PIK3CA and AKT2 mutations in a variety of cancers indicates their important involvement in carcinogenesis. Therefore, we investigated their mutation frequencies in gastric cancer (GC) in China. In our study, we selected hot-spot related exons 9, 18 and 20 of PIK3CA and kinase domain exons 6-14 of AKT2 genes were screened in 10 GC cell lines, 100 advanced primary GC and matched normal tissues. Denaturing high performance liquid chromatography (DHPLC) and DNA sequencing were used to analyze the mutations in the two genes. Two point mutations in the PIK3CA gene were identified in 4 of 10 GC cell lines and in 4 of 100 GC primary tumors. Two polymorphisms in AKT2 were detected in 19 of 100 GC primary tumors. One point mutation in AKT2 was detected in 1 of 10 GC cell lines and 3 of 100 GC primary tumors but no hot spot variation was detected. Our results indicate that PIK3CA and AKT2 mutations occurred at low frequency in GC, and suggest that the PIK3CA/AKT2 pathway might engage other events during gastric carcinogenesis.
authors.affiliation: Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China.
authors.forename: Qing-Ying
authors.initials: QY
authors.lastname: Zhang
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Cheng
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital/Institute, Beijing 100142, China.
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Li
authors.affiliation: Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, China.
authors.forename: William
authors.initials: W
authors.lastname: Au
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital/Institute, Beijing 100142, China. Electronic address: youyonglu@hsc.pku.edu.cn.
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT2; Gastric cancer; Mutation; PIK3CA