Functional analysis of novel gene mutation identified in clinical sequencing

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07721
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nara Medical University (2021); Kindai University (2019-2020)
• Principal Investigator: Takeda Masayuki 奈良県立医科大学, 医学部, 教授 (20510928)
• Co-Investigator(Kenkyū-buntansha): 西尾 和人 近畿大学, 医学部, 教授 (10208134) ; 坂井 和子 近畿大学, 医学部, 講師 (20580559)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遺伝子パネル / ドライバー遺伝子 / 肺癌

Outline of Final Research Achievements

The gene panel contains genes known to predict efficacy of drug therapy, definitive diagnosis, and prognosis, and can reveal information on gene mutations, deletions, insertions, gene fusions, copy number abnormalities, etc., all at once. In clinical sequencing, variants of uncertain significance (VUS), which are not listed in the knowledge database, are often found. In this study, we used software that can predict the 3D structure of these VUSs to predict the functional changes in them, and were able to predict the emergence of resistance mutations by co-mutation of EGFR gene mutations.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

ドライバー遺伝子陽性肺癌において、遺伝子変異別の複数の分子標的薬が承認されているが、それぞれのドライバー遺伝子陽性症例に於いて、分子標的薬の治療効果に症例間格差があり、また耐性機序も異なる。我々は遺伝子パネル検査を用い、各症例に於ける治療前の組織を用い、Co-mutationの有無及びその機能を評価することで、耐性化の機序が異なることを見出した。このようなデータは、今後耐性遺伝子の出現の予測や耐性克服の研究にもつながる。