title: Acquired resistance L747S mutation in an epidermal growth factor receptor-tyrosine kinase inhibitor-naïve patient: A report of three cases.
abstract: The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions inEGFRgenes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have twoEGFRmutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had theEGFRmutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had theEGFRmutation, L747S. Thus, theEGFRmutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of anEGFRmutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan ; Department of Clinical Pathology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Yamaguchi
authors.affiliation: Department of Clinical Pathology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Fukuchi
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takayasu
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Tazawa
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan ; Department of Clinical Pathology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tateno
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kato
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Wakabayashi
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Fujimori
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tsuchiya
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yamashita
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Department of Respiratory Medicine, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama 227-8501, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kokubu
keywords: L747S; epidermal growth factor receptor-tyrosine kinase inhibitor resistance mutation; small cell lung carcinoma