Familial pathogenesis of lung cancer with the epidermal growth factor receptor (EGFR) gene mutation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659399
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: KIKUCHI Toshiaki 東北大学, 医学(系)研究科(研究院), 非常勤講師 (10280926)
• Co-Investigator(Renkei-kenkyūsha): MATSUBARA Yoichi , 国立成育医療研究センター, 所長 (00209602) ; INOUE Akira 東北大学, 病院, 准教授 (70361087) ; SAKAKIBARA Tomohiro 東北労災病院, 副部長 (80422111)
• Research Collaborator: TODE Naoki 東北大学, 病院, 医員 ; HIRANO Taizou 東北大学, 大学院医学系研究科, 非常勤講師
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 家族性癌

Outline of Final Research Achievements

Lung cancer is globally the leading cause of cancer death with the estimated number of the annual deaths as around 1.4 million. Cigarette smoking is a predominant etiological factor of lung carcinogenesis. Further attention has been paid to a growing number of lung carcinomas occurring in never-smokers, suggesting a biologically different disease with a genetic susceptibility. In this regard, the epidermal growth factor receptor (EGFR) gene mutation is more frequent in lung adenocarcinomas of never smokers. In this study, we acquired two 2-generational pedigrees containing more than 2 family members affected with lung adenocarcinoma with EGFR gene mutations, and performed exome capture and sequencing of whole-blood DNA. A de novo mutation was identified in lung cancer patients, but was not in two control subjects. The mutation alters the amino acid sequence, and confers dominant-negative activity that potentially underlies the pathogenesis of EGFR-mutated lung adenocarcinoma.

Free Research Field

呼吸器内科学