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

被引：390

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 ; 090102 ;

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

[1] Characterization of a conserved structural determinant controlling protein kinase sensitivity to selective inhibitors [J].

Blencke, S ;

Zech, B ;

Engkvist, O ;

Greff, Z ;

Örfi, L ;

Horváth, Z ;

Kéri, G ;

Ullrich, A ;

Daub, H .

CHEMISTRY & BIOLOGY, 2004, 11 (05) :691-701

[2] Mutation of threonine 766 in the epidermal growth factor receptor reveals a hotspot for resistance formation against selective tyrosine kinase inhibitors [J].

Blencke, S ;

Ullrich, A ;

Daub, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (17) :15435-15440

[3] Strategies to overcome resistance to targeted protein kinase inhibitors [J].

Daub, H ;

Specht, K ;

Ullrich, A .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (12) :1001-1010

[4] Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib [J].

Han, SW ;

Kim, TY ;

Hwang, PG ;

Jeong, S ;

Kim, J ;

Choi, IS ;

Oh, DY ;

Kim, LH ;

Kim, DW ;

Chung, DH ;

Im, SA ;

Kim, YT ;

Lee, JS ;

Heo, DS ;

Bang, YJ ;

Kim, NK .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (11) :2493-2501

[5] EGFR mutation and resistance of non-small-cell lung cancer to gefitinib [J].

Kobayashi, S ;

Boggon, TJ ;

Dayaram, T ;

Janne, PA ;

Kocher, O ;

Meyerson, M ;

Johnson, BE ;

Eck, MJ ;

Tenen, DG ;

Halmos, B .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (08) :786-792

[6] Mutations of the epidermal growth factor receptor gene in lung cancer:: Biological and clinical implications [J].

Kosaka, T ;

Yatabe, Y ;

Endoh, H ;

Kuwano, H ;

Takahashi, T ;

Mitsudomi, T .

CANCER RESEARCH, 2004, 64 (24) :8919-8923

[7] Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer - A randomized trial [J].

Kris, MG ;

Natale, RB ;

Herbst, RS ;

Lynch, TJ ;

Prager, D ;

Belani, CP ;

Schiller, JH ;

Kelly, K ;

Spiridonidis, H ;

Sandler, A ;

Albain, KS ;

Cella, D ;

Wolf, MK ;

Averbuch, SD ;

Ochs, JJ ;

Kay, AC .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 290 (16) :2149-2158

[8] Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib [J].

Kwak, EL ;

Sordella, R ;

Bell, DW ;

Godin-Heymann, N ;

Okimoto, RA ;

Brannigan, BW ;

Harris, PL ;

Driscoll, DR ;

Fidias, P ;

Lynch, TJ ;

Rabindran, SK ;

McGinnis, JP ;

Wissner, A ;

Sharma, SV ;

Isselbacher, KJ ;

Settleman, J ;

Haber, DA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (21) :7665-7670

[9] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib [J].

Lynch, TJ ;

Bell, DW ;

Sordella, R ;

Gurubhagavatula, S ;

Okimoto, RA ;

Brannigan, BW ;

Harris, PL ;

Haserlat, SM ;

Supko, JG ;

Haluska, FG ;

Louis, DN ;

Christiani, DC ;

Settleman, J ;

Haber, DA .

NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (21) :2129-2139

[10] EGFR mutations in lung cancer:: Correlation with clinical response to gefitinib therapy [J].

Paez, JG ;

Jänne, PA ;

Lee, JC ;

Tracy, S ;

Greulich, H ;

Gabriel, S ;

Herman, P ;

Kaye, FJ ;

Lindeman, N ;

Boggon, TJ ;

Naoki, K ;

Sasaki, H ;

Fujii, Y ;

Eck, MJ ;

Sellers, WR ;

Johnson, BE ;

Meyerson, M .

SCIENCE, 2004, 304 (5676) :1497-1500

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