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

Bell, D. W., Gore, I., Okimoto, R. A., Godin-Heymann, N., Sordella, R., Mulloy, R., Sharma, S. V., Brannigan, B. W., Mohapatra, G., Settleman, J., Haber, D. A. (December 2005) Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nature Genetics, 37 (12). pp. 1315-6. ISSN 1061-4036

URL: http://www.ncbi.nlm.nih.gov/pubmed/16258541
DOI: 10.1038/ng1671

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Antineoplastic Agents pharmacology therapeutic use Carcinoma Non Small Cell Lung drug therapy enzymology genetics Drug Resistance Neoplasm genetics Female Genetic Predisposition to Disease Germ-Line Mutation Humans Lung Neoplasms drug therapy enzymology genetics Male Methionine genetics Middle Aged Pedigree Protein Kinase Inhibitors pharmacology therapeutic use Protein Tyrosine Kinases antagonists & inhibitors Receptor Epidermal Growth Factor genetics Threonine genetics
Subjects: diseases & disorders > cancer > drugs and therapies
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > EGFR
diseases & disorders > cancer > cancer types > lung cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Sordella lab
Depositing User: CSHL Librarian
Date: December 2005
Date Deposited: 24 Apr 2012 15:47
Last Modified: 13 Mar 2013 16:03
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26249

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