Mapping EGFR1 mutations in patients with lung adenocarcinoma.
BACKGROUND
Unselected lung cancer patients seem unable to gain in terms of survival from treatment with epidermal growth factor receptor (EGFR) inhibitors. Screening for specific molecular targets involves detection of EGFR1 mutations. The aim of our study was to develop a simple set of tests to detect mutations at the tyrosine kinase domain of the EGFR1 gene while avoiding expensive DNA sequencing to select patients eligible for treatment.


METHODS
DNA samples from 85 adenocarcinoma patients were analyzed. The cohort consisted of 65 female (40 nonsmokers and 25 smokers) and 20 male patients [15 smokers and 5 diagnosed with bronchioloalveolar carcinomas (BAC)]. Different restriction enzymes were identified that recognize mutations at the EGFR1's tyrosine kinase domain. Biocomputing and polymerase chain reaction were used to develop molecular screening tools.


RESULTS
Eight mutations were found in 7 patients, of which 5 were female nonsmokers (14.3%), 1 was a male nonsmoker, and 1 a male smoker. Among the mutations that were discovered, 5 (71%) were found at exon 19 and 3 (29%) at exon 20. At exon 19, 4 were deletions found in nonsmoker women, whereas the fifth was a deletion-insertion found in a nonsmoker male patient with BAC. At exon 20, 3 mutations were identified in 2 patients: a duplication (in a nonsmoker woman) and 2 substitutions (in a smoker male with BAC). No mutations were found at exons 18 and 21. Gene copy number was increased in 6 patients (4 female and 2 male) with the highest being found in a smoking female patient diagnosed with BAC.


CONCLUSIONS
Mapping of EGFR1 mutations by alternative methods should be used in the screening of patients with non-small cell lung cancer who are candidates for EGFR inhibitor treatment. Patients with an increased EGFR1 copy number could benefit from the monoclonal antibody therapy.
Centre of Respiratory Insufficiency, Athens Chest Diseases Hospital Sotiria, Greece.
Fotis
F
Vlastos
Julie
J
Zinszner
Thomas
T
Hussenet
Stanislas
S
du Manoir
Leonidas
L
Vordonis
Sofia
S
Nikolakopoulou
Georgia
G
Hardavella
Stéfanie
S
Lacomme
Jean Michel
JM
Vignaud
Nadine
N
Martinet
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D015331:Cohort Studies; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004262:DNA Restriction Enzymes / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D004247:DNA; C512478:EGFR protein, human; D066246:ErbB Receptors; D004262:DNA Restriction Enzymes