Molecular pathology of EGFR-mutated lung adenocarcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15086
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Yokohama City University
• Principal Investigator: MATSUMURA Mai 横浜市立大学, 医学部, 助教 (50812997)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: EGFR変異肺腺癌 / MUC21 / 微小乳頭状亜型 / 全エクソーム解析 / バイオインフォマティクス解析

Outline of Final Research Achievements

Our recent study demonstrated that malignant grade of EGFR-mutated lung adenocarcinoma (LADC) was determined by micropapillary (mPAP) element. I revealed that MUC21 was related to mPAP element of EGFR-mutated LADCs, and the tumors expressed MUC21 protein had poor prognosis. To uncover the potential molecular basis of mPAP element, I investigated somatic mutations specific to mPAP element in EGFR-mutated LADC. mPAP and other elements were separately collected from frozen tissue sections of EGFR-mutated LADC by the laser capture microdissection system and were subjected to whole exomes sequencing analyses. Through bioinformatics analysis, somatic mutations which was cofirmed by sanger-sequencing specific to mPAP elements were identified. Finally, I made “Highly malignant EGFR-mutated LADCs gene panel”. These gene mutations might be related to the highly malignant activity of mPAP element.

Free Research Field

肺病理

Academic Significance and Societal Importance of the Research Achievements

これまで肺がん臨床の現場で分子治療標的となる遺伝子変異は、腫瘍発生に関わるドライバー変異であった。我々が作成した「高悪性度EGFR肺腺癌パネル」に含まれる後発変異が治療標的となれば、EGFRチロシンキナーゼ阻害薬（EGFR-TKI）との併用により、腫瘍の悪性化や薬剤耐性化の阻止に役立つ可能性がある。