Whole genome gene copy number profiling of gastric cancer identifies <i>PAK1</i> and <i>KRAS</i> gene amplification as therapy targets

DOI Web Site Web Site 被引用文献2件
  • Ziliang Qian
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Guanshan Zhu
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Lili Tang
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Mei Wang
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Lianhai Zhang
    Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Beijing Cancer Hospital and Institute Beijing 100142 China
  • Jiangang Fu
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Chunlei Huang
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Shuqiong Fan
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Yun Sun
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Jing Lv
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Hua Dong
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Beirong Gao
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Xinying Su
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Dehua Yu
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Jie Zang
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Xiaolin Zhang
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China
  • Jiafu Ji
    Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Beijing Cancer Hospital and Institute Beijing 100142 China
  • Qunsheng Ji
    Innovation Centre China, Asia & Emerging Market iMed, AstraZeneca Innovation Medicines and Early Development 199 Liangjing Road, Zhangjiang Hi‐Tech Park Shanghai 201203 People's Republic Of China

書誌事項

公開日
2014-06-17
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/gcc.22196
公開者
Wiley

この論文をさがす

説明

<jats:p>Gastric cancer is the second leading cause of death from cancer worldwide, with an approximately 20% 5‐year survival rate. To identify molecular subtypes associated with the clinical prognosis, in addition to genetic aberrations for potential targeted therapeutics, we conducted a comprehensive whole‐genome analysis of 131 Chinese gastric cancer tissue specimens using whole‐genome array comparative genomic hybridization. The analyses revealed gene focal amplifications, including <jats:italic>CTSB</jats:italic>, <jats:italic>PRKCI</jats:italic>, <jats:italic>PAK1</jats:italic>, <jats:italic>STARD13, KRAS</jats:italic>, and <jats:italic>ABCC4</jats:italic>, in addition to <jats:italic>ERBB2</jats:italic>, <jats:italic>FGFR2</jats:italic>, and <jats:italic>MET</jats:italic>. The growth of <jats:italic>PAK1‐</jats:italic>amplified gastric cancer cells in vitro and in vivo was inhibited when the corresponding mRNA was knocked down. Furthermore, both <jats:italic>KRAS</jats:italic> amplification and <jats:italic>KRAS</jats:italic> mutation were identified in the gastric cancer specimens. <jats:italic>KRAS</jats:italic> amplification was associated with worse clinical outcomes, and the <jats:italic>KRAS</jats:italic> gene mutation predicted sensitivity to the MEK1/2 inhibitor AZD6244 in gastric cancer cell lines. In summary, amplified <jats:italic>PAK1</jats:italic>, as well as <jats:italic>KRAS</jats:italic> amplification/mutation, may represent unique opportunities for developing targeted therapeutics for the treatment of gastric cancer. © 2014 Wiley Periodicals, Inc.</jats:p>

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