title: Mutation of the epidermal growth factor receptor gene in the development of adenocarcinoma of the lung.
abstract: Recently, a mutation of the epidermal growth factor receptor (EGFR) gene has been reported to be implicated in the development of pulmonary adenocarcinoma. However, the involvement of the mutation in atypical adenomatous hyperplasia (AAH) and multiple adenocarcinomas still remains unclear. We herein examined the EGFR mutations in 9 AAH and 31 adenocarcinoma lesions obtained from 30 Japanese patients. Nine patients had synchronous or metachronous multiple adenocarcinomas and/or AAH. Mutations in exons 18-21 of EGFR gene were analysed using polymerase chain reaction and direct sequence methods. EGFR mutations were detected in 4 (44%) of 9 AAH and in 7 (23%) of 31 adenocarcinomas. A gefitinib-resistant point mutation (T790M) in exon 20 without gefitinib treatment was detected in 1 AAH and 1 adenocarcinoma. The patient with T790M mutated AAH, which also had an exon 19 mutation of D761Y, had synchronous adenocarcinoma, which had only an exon 19 mutation of D761Y. The other exon 19 mutations were all in-frame deletions. In the two patients with synchronous AAH and adenocarcinoma, AAH had mutations at exon 19 although adenocarcinoma did not have any mutations. In the patient with synchronous 2 adenocarcinomas, each had different mutations (exons 19 and 21). In two patients with double adenocarcinomas, 1 adenocarcinoma harbored exon 21 mutations, while the other demonstrated no mutations. Although EGFR mutations appeared to be partially associated with the early steps of adenocarcinoma development, such mutations may possibly occur randomly even in multiple lesions in a single patient.
authors.affiliation: Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kozuki
authors.forename: Akiko
authors.initials: A
authors.lastname: Hisamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Nagio
authors.initials: N
authors.lastname: Takigawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Segawa
authors.forename: Masao
authors.initials: M
authors.lastname: Nakata
authors.forename: Koichi
authors.initials: K
authors.lastname: Mandai
authors.forename: Kenji
authors.initials: K
authors.lastname: Eguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D018255:Adenomatosis, Pulmonary / Q000188:drug therapy / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005091:Exons; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib