Gastric cancer is the one of the major cause of cancer-related death,especially in Asia.Gastric adenocarcinoma,the most common type of gastric cancer,is heterogeneous and its incidence and cause varies widely with geographical regions,gender,ethnicity,and diet.Since unique mutations have been observed in individual human cancer sample,identification and characterization of the molecular alterations underlying individual gastric adenocarcinoma is a critical step for developing more effective,personalized therapies.Until recently,identifying genetic mutations in an individual basis by DNA sequencing remains a daunting task.The recent advance of new next-generation DNA sequencing technologies,such as the semiconductor-based Ion Torrent sequencing platform,makes DNA sequencing cheaper,faster and more reliable.In this study,we aim to identify genetic mutations in the genes,which are targeted by drugs in the clinical use or under development,in individual human adenocarcinoma sample by using Ion Torrent sequencing.We sequenced 739 loci from 46 cancer-related genes in 242 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel.The sequencing analysis revealed frequent mutations in MLH1 (8.3%),MET (11.2%),KIT (21.5%),and PIK3CA (40.5%) genes in the human gastric adenocarcinomic samples.Many mutations that are not previously reported in gastric adenocarcinomas were also identified.Moreover,distinctive patterns and the combination of mutations in various sets of genes,including HER2,EGFR,MET,FGFR,PI3K/MTOR,MLH1,MET,KIT,PIK3CA,and P53,were also identified in these gastric adenocarcinoma samples.Thus,this study indicates the necessity of sequencing individual human adenocarcinoma in order to match the use of personalized single targeted drugs or two or more targeted drugs in combination against individual adenocarcinoma-specific mutations.
gastric adenocarcinoma genetic mutations targeted therapy Ion Torrent sequencing cancer panel personalized medicine
XU Zhi DONG Haichao ZHANG Guangchun LIU Zhiyuan DONG Zhishou GUO Baishuai YAN He YAN Chaowei WANG Lu SU Ziyi LI Yangyang HUO Xinying GU Dongying ZHANG Xiaojing WU Xiaomin WEI Xiaowei HONG Lingzhi ZHANG Yangmei YANG Jinsong GONG Yonglin TANG Cuiju Lindsey JONES YE Hua HUANG Xue CHEN Siyi CHEN Jinfei TANG Chuanning Vijayalakshmi NANDAKUMAR LOU Feng ZHANG Dandan JIANG Shouwen SUN Hong
Department of Oncology,The Affiliated Nanjing First Hospital,Nanjing Medical University,Nanjing 2100 San Valley Biotechnology Inc.,Beijing 100044,China Norris Comprehensive Cancer Center,Department of Molecular Microbiology and Immunology,Keck School o