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学科主题: 临床医学
题名:
Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer
作者: Wang, Shuhang1; An, Tongtong1; Duan, Jianchun1; Zhang, Lijian2; Wu, Meina1; Zhou, Qinghua3; Chen, Jinfeng2; Zhuo, Minglei1; Yang, Lu1; Wang, Yuyan1; Bai, Hua1; Wang, Jie1
刊名: PLOS ONE
发表日期: 2013-03-08
DOI: 10.1371/journal.pone.0051021
卷: 8, 期:3
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: FACTOR RECEPTOR MUTATIONS ; MET AMPLIFICATION ; GEFITINIB ; ERLOTINIB ; TUMORS ; SENSITIVITY ; RESISTANCE
英文摘要:

Introduction: Genetic aberrancies within epidermal growth factor receptor (EGFR) pathway are associated with therapeutic outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, the impact of chemotherapy on EGFR-related genes alterations has not been defined in NSCLC. Our study aims to investigate the impact of neoadjuvant chemotherapy (Neoadj-Chemo) on EGFR activating mutations and associated EGFR-TKIs resistance-related genes.

Patients and Methods: Matched tumor samples were obtained retrospectively from 66 NSCLC patients (stages IIb-IIIb) corresponding to pre-and post-Neoadj-Chemo. EGFR mutations were detected by denaturing high performance liquid chromatography (DHPLC) and confirmed by Amplification Refractory Mutation System technology (ARMS), KRAS mutations, T790M mutation and c-MET amplification were identified using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), ARMS, and real-time PCR, respectively.

Results: Before Neoadj-Chemo, EGFR mutations were identified in 33.3% (22/66) of NSCLC patients. Only 18.2% (12/66) of patients carried EGFR mutations after Neoadj-Chemo (p = 0.013). The median peak value of EGFR 19 exon mutations decreased non-significantly after Neoadj-Chemo. KRAS mutation rate decreased from 4.6% (3/66) to 3.0% (2/66) with Neoadj-Chemo. Although the overall percentage of patients exhibiting c-MET amplifications (6.1% [4/66]) did not change with Neoadj-Chemo, two patients transitioned from negative to positive c-MET amplification, and two patients reversed these changes post-Neoadj-Chemo. T790M mutations were absent from all samples.

Conclusion: Neoadjuvant chemotherapy tends to decrease the mutation frequency of EGFR mutation and downstream genes, which suggests that real-time samples analysis for genetic aberrancies within EGFR pathways have important value to delineate specific patient populations and facilitate individualized treatment.

语种: 英语
所属项目编号: 81025012 ; 81172235 ; 2007-1023 ; 2011-2-22 ; Z090507017709015 ; 81101726
项目资助者: National Natural Sciences Foundation Distinguished Young Scholars ; National Natural Sciences Foundation General Program ; Capital Development Foundation ; Beijing Health Systems Academic Leader ; Science and Technology Project of Beijing ; National Natural Sciences Foundation China Youth Science Foundation
WOS记录号: WOS:000318679900001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67459
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Sch Oncol, Dept Thorac Med Oncol,Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China
2.Peking Univ, Sch Oncol, Dept Thorac Surg,Beijing Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100871, Peoples R China
3.Tianjin Med Univ Gen Hosp, Dept Thorac Surg, Tianjin, Peoples R China

Recommended Citation:
Wang, Shuhang,An, Tongtong,Duan, Jianchun,et al. Alterations in EGFR and Related Genes following Neo-Adjuvant Chemotherapy in Chinese Patients with Non-Small Cell Lung Cancer[J]. PLOS ONE,2013,8(3).
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