title: Frequent KIT mutations in human gastrointestinal stromal tumors.
abstract: Identifying gene mutations in individual tumors is critical to improve the efficacy of cancer therapy by matching targeted drugs to specific mutations. Gastrointestinal stromal tumors (GIST) are stromal or mesenchymal subepithelial neoplasms affecting the gastrointestinal tract and frequently contain activating gene mutations in either KIT or platelet-derived growth factor A (PDGFRA). Although GIST is highly responsive to several selective tyrosine kinase inhibitors, combined use of inhibitors targeting other mutations is needed to further prolong survival in patients with GIST. In this study, we aim to screen and identify genetic mutations in GIST for targeted therapy using the new Ion Torrent next-generation sequencing platform. Utilizing the Ion Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes using DNA extracted from formalin-fixed and paraffin-embedded (FFPE) samples of 121 human gastrointestinal stromal tumors, set up stringent parameters for reliable variant calling by filtering out potential raw base calling errors, and identified frequent mutations in the KIT gene. This study demonstrates the utility of using Ion Torrent sequencing to efficiently identify human cancer mutations. This may provide a molecular basis for clinically developing new drugs targeting these gene mutations for GIST therapy.
authors: 1] Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China [2].
authors: Zhi
authors: Z
authors: Xu
authors: 1] Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China [2].
authors: Xinying
authors: X
authors: Huo
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Chuanning
authors: C
authors: Tang
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Hua
authors: H
authors: Ye
authors: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors: Vijayalakshmi
authors: V
authors: Nandakumar
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Feng
authors: F
authors: Lou
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Dandan
authors: D
authors: Zhang
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Shouwen
authors: S
authors: Jiang
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Hong
authors: H
authors: Sun
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Haichao
authors: H
authors: Dong
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Guangchun
authors: G
authors: Zhang
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Zhiyuan
authors: Z
authors: Liu
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Zhishou
authors: Z
authors: Dong
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Baishuai
authors: B
authors: Guo
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: He
authors: H
authors: Yan
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Chaowei
authors: C
authors: Yan
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Lu
authors: L
authors: Wang
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Ziyi
authors: Z
authors: Su
authors: San Valley Biotechnology Inc., Beijing 100044, China.
authors: Yangyang
authors: Y
authors: Li
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Dongying
authors: D
authors: Gu
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Xiaojing
authors: X
authors: Zhang
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Xiaomin
authors: X
authors: Wu
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Xiaowei
authors: X
authors: Wei
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Lingzhi
authors: L
authors: Hong
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Yangmei
authors: Y
authors: Zhang
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Jinsong
authors: J
authors: Yang
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Yonglin
authors: Y
authors: Gong
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Cuiju
authors: C
authors: Tang
authors: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors: Lindsey
authors: L
authors: Jones
authors: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors: Xue F
authors: XF
authors: Huang
authors: Norris Comprehensive Cancer Center, Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors: Si-Yi
authors: SY
authors: Chen
authors: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors: Jinfei
authors: J
authors: Chen
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D019009:Proto-Oncogene Proteins c-kit