De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma

• Material Type: 博士論文
• Title: De Novo T790M Mutation in an L858R Epidermal Growth Factor Receptor Mutant-Associated Lung Adenocarcinoma
• Author/Editor: Fujiwara, Takumi
• Author Heading: Fujiwara, Takumi
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2021-03-25
• Publication Date (W3CDTF): 2021-03-25
• Degree grantor/type: 三重大学
• Date Granted: 2021-03-25
• Date Granted (W3CDTF): 2021-03-25
• Dissertation Number: 甲医学第2056号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第2056号
• Text Language Code: eng
• Alias of Author: フジワラ, タクミ; 藤原, 拓海
• Subject Heading: epidermal growth factor receptor; driver mutations; lung adenocarcinoma; drug resistance; tyrosine kinase inhibitor
• Target Audience: 一般
• Note (General): application/pdf; Background: Lung cancer is the leading cause of mortality for cancer worldwide. A point mutation in exon 21 of the epidermal growth factor receptor resulting in the substitution of arginine for leucine at position 858 (L858R) is a frequent cause of lung adenocarcinoma. Tyrosine kinase inhibitors are effective for treating patients with lung cancer associated with mutant epidermal growth factor receptors but most tumors become resistant shortly after treatment. The substitution of methionine for threonine at position 790 (T790M) on exon 20 is the most frequently acquired mutation leading to resistance to tyrosine kinase inhibitors. Whether the T790M mutation occurred after tyrosine kinase inhibitor therapy or it already existed before therapy is unclear. Methods: Here, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. Results: The L858R mutation-associated lung adenocarcinoma acquired de novo T790 mutation without previous therapy. Conclusions: The results of this study suggest that lung tumors may spontaneously acquire T790M mutations without any drug-related selective pressure.; 本文/Department of Pulmonary and Critical Care Medicine, Graduate School of Medicine, Mie University, Mie, Edobashi 2-174, Tsu, Mie 514-8507, Japan; 13p
• DOI: info:doi/10.3390/cancers12103074; https://doi.org/info:doi/10.3390/cancers12103074
• Persistent ID (NDL): info:ndljp/pid/11711071; https://dl.ndl.go.jp/pid/11711071
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-08-09T17:15:52+09:00
• Date Created (W3CDTF): 2021-06-29
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10076/00019688; https://mie-u.repo.nii.ac.jp/records/14070
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp