Mutational analysis on carcinogenesis in multiple primary lung cancers

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Osaka City University
• Principal Investigator: Kawaguchi Tomoya 大阪市立大学, 大学院医学研究科, 教授 (70254422)
• Co-Investigator(Kenkyū-buntansha): 洪 泰浩 和歌山県立医科大学, 医学部, 准教授 (80426519)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肺癌 / 発がん / 環境因子 / ゲノム解析

Outline of Final Research Achievements

We performed paired mutational analyses to clarify genetic mutations in multiple primary lung cancers (MPLC) and its relationship with environmental factors.
We obtained 38 surgical specimens from 17 patients who were pathologically diagnosed as MPLC and underwent surgery at Osaka City University Hospital. For genetic profiling of MPLC patients, the extracted DNAs were deep-sequenced for somatic mutations in 409 cancer-associated genes. The occurrence of concomitant EGFR or KRAS mutations in multiple tumors within the same individuals was significantly more frequent than expected by chance, suggesting environmental factors play more role in EGFR and KRAS mutations than the other mutations including TP53 which occurred more randomly in individual tumors. The development of EGFR or KRAS-mutated tumors were strongly related to environmental factors such as sex and smoking history, and suggested that the other mutations may occur randomly.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

肺がん発癌に関与する環境因子としては喫煙がよく知られているが、喫煙によるゲノム異常から発癌へ至るメカニズムや、その他の環境因子の発癌における関与についての詳細は未だ明らかではない。本研究では肺がん発癌における環境因子の関与をさらに解明するために、同一症例における異所性、異時性同時性に発生した多発肺がん検体を用いてゲノム相同性の解析を行った。同じ環境因子下で発生した異なる肺がんの分子生物学的差異を明らかにし、発癌における環境因子の役割を解明する一助となった。