Τίτλος:
Mapping EGFR1 mutations in patients with lung adenocarcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
INTRODUCTION: 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 EGFR1s 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. CONCLUSION: 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. Copyright © 2010 by Lippincott Williams & Wilkins.
Συγγραφείς:
Vlastos, F.
Zinszner, J.
Hussenet, T.
Du Manoir, S.
Vordonis, L.
Nikolakopoulou, S.
Hardavella, G.
Lacomme, S.
Vignaud, J.M.
Martinet, N.
Περιοδικό:
Diagnostic Molecular Pathology
Λέξεις-κλειδιά:
epidermal growth factor receptor; epidermal growth factor receptor 1; epidermal growth factor receptor antibody; protein tyrosine kinase; unclassified drug, adult; aged; article; controlled study; DNA sequence; exon; female; gene amplification; gene deletion; gene dosage; gene mapping; gene mutation; genetic screening; human; human tissue; lung adenocarcinoma; lung alveolus cell carcinoma; major clinical study; male; polymerase chain reaction; priority journal; single nucleotide polymorphism; smoking, Adenocarcinoma; Aged; Cohort Studies; DNA; DNA Restriction Enzymes; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Receptor, Epidermal Growth Factor
DOI:
10.1097/PDM.0b013e3181d32605
