Identification of EGFR mutations in esophageal cancer
Identification of EGFR mutations in esophageal cancer
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DOI：
10.1016/j.ejso.2006.10.034
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发表时间：
2007-02-01
期刊：
影响因子：
3.8
通讯作者：
Mori, M.
中科院分区：
文献类型：
--
作者：
Sudo, T.;Mimori, K.;Mori, M.
背景：众所周知，食道癌的预后比其他消化系统肿瘤差，尽管采取了多种治疗方法，但这一状况亟待改善。表皮生长因子受体(EGFR)抑制剂吉非替尼在日本已被批准用于治疗晚期非小细胞肺癌患者，此后有多篇论文报道了成功治疗的患者存在EGFR基因突变的情况。目的：本研究的目的是研究EGFR突变在食管癌细胞系和原发病变中的存在，并探讨吉非替尼治疗食道癌的可能性。材料和方法：培养19株食管癌细胞株，采用超速离心法提取DNA。采集50例原发癌组织和相应的正常组织标本，采用相同的方法提取DNA。结果：19个细胞株中有3个细胞株存在相同的21607位核苷酸沉默突变，即外显子20的G-to-A突变。50例患者中有1例在第719位密码子发生突变，导致从甘氨酸到天冬氨酸的氨基酸替代。结论：食管癌中表皮生长因子受体基因突变很少见，但确实存在突变，因此，通过选择具有这种突变的患者，吉非替尼可用于食管癌的治疗方案。(C)2006爱思唯尔有限公司。保留所有权利。
Background: It is well known that the prognosis for esophageal cancer is worse than for other digestive cancers in spite of multimodality treatment, and there is an urgent need to improve this situation. The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, was approved in Japan to treat advanced non-small cell lung cancer patients and several papers have since reported that the successfully treated patients had genetic mutations in EGFR.Purpose: The aim of this study was to investigate the existence of EGFR mutations in esophageal cancer cell lines and primary lesions, and also to explore the possibility of treating esophageal cancer using gefitinib.Materials and Methods: Nineteen esophageal cancer cell lines were cultured and DNA was extracted using an ultracentrifugation method. Fifty cases of primary cancer and corresponding normal tissue samples were obtained and DNA was extracted using the same protocol. Nested PCR and DNA sequencing targeting exons 18, 19, 20 and 21 of EGFR were performed to investigate the presence of mutations in esophageal cancer cell lines and primary tumors.Results: Three of the 19 cell lines had the same silent mutation at nucleotide 21607, a G-to-A substitution in exon 20. One of the 50 patients had an EGFR mutation in codon 719, resulting in an amino acid substitution from glycine to aspartic acid.Conclusion: EGFR mutations in esophageal carcinoma are rare but do exist, and thus gefitinib could be included in esophageal cancer treatment regimens by selecting those patients who possess such mutations. (C) 2006 Elsevier Ltd. All rights reserved.