Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR

被引：411

作者：

Bell, DW

Gore, I

Okimoto, RA

Godin-Heymann, N

Sordella, R

Mulloy, R

Sharma, SV

Brannigan, BW

Mohapatra, G

Settleman, J

Haber, DA

机构：

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[2] St Vincents Hosp, Bruno Canc Ctr, Birmingham, AL 35205 USA

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA

来源：

NATURE GENETICS | 2005年 / 37卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ng1671

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学]; 090102 [作物遗传育种];

摘要：

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.

引用

页码：1315 / 1316

页数：2

共 15 条

[11]

Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain [J].