Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas
Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas
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DOI：
10.1158/1078-0432.ccr-05-0976
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发表时间：
2006-01-01
影响因子：
11.5
通讯作者：
Lee, SH
中科院分区：
文献类型：
--
作者：
Lee, JW;Soung, YH;Lee, SH
目的：最近的报道显示，ERBB2基因的激酶结构域在肺腺癌中发生了体突变，表明突变的ERBB2基因是人类癌症的致癌基因。然而，由于先前的报道主要将ERBB2的突变搜索集中在肺癌上，因此其他类型的人类癌症中ERBB2突变的数据在很大程度上是未知的。实验设计：在这里，我们用PCR单链构象多态性方法对胃癌、结直肠癌和乳腺癌组织中的ERBB2激酶结构域进行了突变分析。结果：180例胃癌中有9例（5.0%）、104例结直肠癌中有3例（2.9%）、94例乳腺癌中有4例（4.3%）检测到ERBB2激酶结构域突变。除1个帧内缺失突变外，检测到的ERBB2突变均为错义突变。在检测到的16个ERBB2突变中，4个影响外显子20位点的Val(777)， 3个影响外显子19位点的Leu（755）。我们同时分析了16例ERBB2突变样本中EGFR、K-RAS、PIK3CA和BRAF基因的体细胞突变，发现3例ERBB2突变的结直肠癌样本均存在K-RAS突变。结论：本研究发现，除肺腺癌外，ERBB2激酶结构域突变还发生在胃癌、乳腺癌、结直肠癌等其他常见的人类癌症中，提示ERBB2单独突变或与K-RAS突变共同改变ERBB2介导的信号通路可能参与了人类癌症的发生发展。
Purpose: Recent reports revealed that the kinase domain of the ERBB2 gene is somatically mutated in lung adenocarcinoma, suggesting the mutated ERBB2 gene as an oncogene in human cancers. However, because previous reports focused the mutational search of ERBB2 primarily on lung cancers, the data on ERBB2 mutations in other types of human cancers have been largely unknown.Experimental Design: Here, we did a mutational analysis of the ERBB2 kinase domain by PCR single-strand conformational polymorphism assay in gastric, colorectal, and breast carcinoma tissues.Results: We detected the ERBB2 kinase domain mutations in 9 of 180 gastric carcinomas (5.0%), in 3 of 104 colorectal carcinomas (2.9%), and in 4 of 94 breast carcinomas (4.3%). All of the detected ERBB2 mutations except for one in-frame deletion mutation were missense mutations. Of the 16 ERBB2 mutations detected, 4 affected Val(777) in the exon 20 site, and 3 affected Leu(755) in the exon 19 site. We simultaneously analyzed the somatic mutations of EGFR, K-RAS, PIK3CA, and BRAF genes in the 16 samples with ERBB2 mutations, and found that all of the 3 colorectal carcinoma samples with ERBB2 mutations harbored K-RAS mutations.Conclusion: This study showed that in addition to lung adenocarcinomas, ERBB2 kinase domain mutation occurs in other common human cancers such as gastric, breast, and colorectal cancers, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations alone or together with K-RAS mutations may contribute to the development of human cancers.