Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR
Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR
复制标题
DOI：
10.1038/ng1671
复制
发表时间：
2005-12-01
期刊：
影响因子：
30.8
通讯作者：
Haber, DA
中科院分区：
文献类型：
--
作者：
Bell, DW;Gore, I;Haber, DA
表皮生长因子受体（EGFR）的体细胞激活突变确定了一部分对酪氨酸激酶抑制剂有反应的非小细胞肺癌。耐药性的产生与一种特定的继发性体细胞突变——EGFR T790M有关。在此我们描述了一个有多个非小细胞肺癌病例的家族，其与这种突变的种系传递相关。所分析的六个肿瘤中有四个显示出继发性体细胞激活的EGFR突变，与种系EGFR突变T790M呈顺式出现。这些观察结果表明改变的EGFR信号传导与肺癌的遗传易感性有关。
Somatic activating mutations in EGFR identify a subset of non-small cell lung cancer that respond to tyrosine kinase inhibitors. Acquisition of drug resistance is linked to a specific secondary somatic mutation, EGFR T790M. Here we describe a family with multiple cases of non-small cell lung cancer associated with germline transmission of this mutation. Four of six tumors analyzed showed a secondary somatic activating EGFR mutation, arising in cis with the germline EGFR mutation T790M. These observations implicate altered EGFR signaling in genetic susceptibility to lung cancer.