Somatic mutations of epidermal growth factor receptor in colorectal carcinoma
Somatic mutations of epidermal growth factor receptor in colorectal carcinoma
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DOI：
10.1158/1078-0432.ccr-04-1894
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发表时间：
2005-02-15
影响因子：
11.5
通讯作者：
Mori, M
中科院分区：
文献类型：
--
作者：
Nagahara, H;Mimori, K;Mori, M
目的：表皮生长因子受体（EGFR）基因的体细胞突变可以预测非小细胞肺癌对吉非替尼的敏感性。然而，在结直肠癌中没有突变的报道。因此，我们通过联合使用激光显微解剖和基因组DNA测序来分析结直肠癌中的EGFR突变。实验设计：我们检测了11个具有代表性的结直肠癌细胞系和33个结直肠癌临床样本。在临床病例中，我们仅用激光显微解剖术仔细解剖冰冻切片中的癌细胞。在DNA提取和PCR后，我们通过测序基因组DNA来检测EGFR突变。结果：11个结直肠癌细胞系均未出现体细胞突变，但33个临床肿瘤中有4个（12%）出现EGFR激酶结构域突变。这可能是关于结直肠癌中体细胞突变的首次报道。结论：我们的研究结果表明，少数结直肠腺癌表现出EGFR的体细胞突变，这些肿瘤可能对吉非替尼治疗敏感。
Purpose: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA.Experimental Design: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA.Results: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma.Conclusions: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.