Genomic alterations of non-small-cell lung cancer following radiotherapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Aichi Cancer Center Research Institute (2017-2018); Foundation for Biomedical Research and Innovation (2015-2016)
• Principal Investigator: FUJITA Shiro 愛知県がんセンター(研究所), がん病態生理学分野, 研究員 (60612140)
• Research Collaborator: MASAGO Katsuhiro ; HIRATA Yukio ; YATABE Yasushi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 次世代シークエンサー / 非小細胞肺癌 / 放射線治療

Outline of Final Research Achievements

Definite radiotherapy and/or chemoradiotherapy (RT/CRT) is often conducted for the treatment of non-small cell lung cancer (NSCLC). However, there is a potential concern regarding the mutagenic effects on tumor cells derived from the therapies, and genomic information regarding cancer cells that survived definitive RT/CRT is lacking. To evaluate the mutagenic effect of RT/CRT, we compared genomic signatures of recurrent NSCLC tissue with those of pretreatment. Some mutations remained in the post-therapy state, and others, including driver mutations, either newly occurred or disappeared during the course of disease. Compared with single nucleotide substitution (23.8%), substantial number of deletions (76.2%) was observed in specimens obtained after definite RT/CRT. RT/CRT effects on tumor cells have a wide spectrum, and re-sequencing of a recurrent lesion is always recommended to discuss the best course of therapy for recurrent NSCLC after RT/CRT.

Free Research Field

がんゲノム解析

Academic Significance and Societal Importance of the Research Achievements

非小細胞肺癌の診療においては日常的に、遺伝子変異の情報を得た上で適切な治療法が選択されているが、いつの時点で採取された癌組織を用いて遺伝子解析を行うべきかについては、これまで統一した見解がなかった。今回の研究にて、治療目的で照射された放射線が癌細胞の遺伝子に無視できない変化を与えていることが判明した。今後、特に放射線を含む治療後の患者の診療に際しては、放射線治療後に改めて採取されたがん組織の遺伝子情報を参考にすることが望ましいと考えられる。これは一般診療の質の向上にも繋がる重要な発見といえる。