Bell Daphne W, Gore Ira, Okimoto Ross A, Godin-Heymann Nadia, Sordella Raffaella, Mulloy Roseann, Sharma Sreenath V, Brannigan Brian W, Mohapatra Gayatry, Settleman Jeff, Haber Daniel A
Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, Massachusetts 02129, USA.
Nat Genet. 2005 Dec;37(12):1315-6. doi: 10.1038/ng1671. Epub 2005 Oct 30.
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.
表皮生长因子受体（EGFR）中的体细胞激活突变可识别出对酪氨酸激酶抑制剂有反应的非小细胞肺癌亚群。耐药性的获得与一种特定的继发性体细胞突变——EGFR T790M相关。在此，我们描述了一个家族，其中多例非小细胞肺癌与该突变的种系传递有关。在分析的6个肿瘤中，有4个显示出继发性体细胞激活EGFR突变，与种系EGFR突变T790M顺式发生。这些观察结果表明EGFR信号改变与肺癌的遗传易感性有关。
