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Whole Genome Gene Copy Number Profiling of Gastric Cancer Identifies PAK1 and KRAS Gene Amplification as Therapy Targets
Qian, Ziliang1; Zhu, Guanshan1; Tang, Lili1; Wang, Mei1; Zhang, Lianhai2; Fu, Jiangang1; Huang, Chunlei1; Fan, Shuqiong1; Sun, Yun1; Lv, Jing1; Dong, Hua1; Gao, Beirong1; Su, Xinying1; Yu, Dehua1; Zang, Jie1; Zhang, Xiaolin1; Ji, Jiafu2; Ji, Qunsheng1
刊名GENES CHROMOSOMES & CANCER
2014-11-01
DOI10.1002/gcc.22196
53期:11页:883-894
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Genetics & Heredity
研究领域[WOS]Oncology ; Genetics & Heredity
关键词[WOS]POSITIVE LYMPH-NODES ; PAN-FGFR INHIBITOR ; PHASE-III TRIAL ; MET AMPLIFICATION ; ADENOCARCINOMA ; PROGNOSIS ; CARCINOMA ; OVEREXPRESSION ; SENSITIVITY ; RESECTION
英文摘要

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 CTSB, PRKCI, PAK1, STARD13, KRAS, and ABCC4, in addition to ERBB2, FGFR2, and MET. The growth of PAK1-amplified gastric cancer cells in vitro and in vivo was inhibited when the corresponding mRNA was knocked down. Furthermore, both KRAS amplification and KRAS mutation were identified in the gastric cancer specimens. KRAS amplification was associated with worse clinical outcomes, and the KRAS gene mutation predicted sensitivity to the MEK1/2 inhibitor AZD6244 in gastric cancer cell lines. In summary, amplified PAK1, as well as KRAS amplification/mutation, may represent unique opportunities for developing targeted therapeutics for the treatment of gastric cancer. (c) 2014 Wiley Periodicals, Inc.

语种英语
WOS记录号WOS:000342158500001
引用统计
被引频次:16[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56021
专题北京大学临床肿瘤学院_胃肠肿瘤中心
北京大学临床肿瘤学院_胃肠肿瘤中心一病区
作者单位1.AstraZeneca Innovat Med & Early Dev, Innovat Ctr China Asia & Emerging Market iMed, Shanghai 201203, Peoples R China
2.Beijing Canc Hosp & Inst, Dept Gastrointestinal Surg, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100142, Peoples R China
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Qian, Ziliang,Zhu, Guanshan,Tang, Lili,et al. Whole Genome Gene Copy Number Profiling of Gastric Cancer Identifies PAK1 and KRAS Gene Amplification as Therapy Targets[J]. GENES CHROMOSOMES & CANCER,2014,53(11):883-894.
APA Qian, Ziliang.,Zhu, Guanshan.,Tang, Lili.,Wang, Mei.,Zhang, Lianhai.,...&Ji, Qunsheng.(2014).Whole Genome Gene Copy Number Profiling of Gastric Cancer Identifies PAK1 and KRAS Gene Amplification as Therapy Targets.GENES CHROMOSOMES & CANCER,53(11),883-894.
MLA Qian, Ziliang,et al."Whole Genome Gene Copy Number Profiling of Gastric Cancer Identifies PAK1 and KRAS Gene Amplification as Therapy Targets".GENES CHROMOSOMES & CANCER 53.11(2014):883-894.
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