Expression analysis and search for novel molecular target of the fetal adenocarcinoma of the lung using a reverse phase protein array

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15111
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: The University of Tokyo (2021); Kanagawa Cancer Center Research Institute (2018-2020)
• Principal Investigator: Suzuki Masaki 東京大学, 医学部附属病院, 助教 (00770108)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 高悪性度胎児型腺癌 / 胎児型腺癌 / 肺腺癌 / KMT2C

Outline of Final Research Achievements

High-grade fetal adenocarcinoma of the lung (H-FLAC) is a rare variant of pulmonary adenocarcinoma. Although expression analysis using a reverse phase protein array (RPPA) has planned in this study, we performed RNA-seq analysis because of difficulty of RPPA analysis using formalin fixed paraffin embedded tissues. The RNA-seq analysis showed that KMT2C expression was significantly lower in H-FLACs compared to that in common type pulmonary adenocarcinomas. Immunohistochemical analysis also showed significantly lower levels of KMT2C in H-FLACs compared to that in common type adenocarcinomas. Some H-FLACs showed diffuse p53 expression or aberrant β-catenin nuclear localization. Therefore, it was suggested that KMT2C dysfunction are potentially associated with the biological features of H-FLACs.

Free Research Field

人体病理学

Academic Significance and Societal Importance of the Research Achievements

高悪性度胎児型肺腺癌(H-FLAC)では通常型腺癌に比べてKMT2Cの発現が低下している症例が多いことが明らかとなり，KMT2Cの機能異常が高頻度に生じていることが示唆された．KMT2Cはヒストンメチル化酵素として機能しており，この機能異常に基づくエピゲノム異常がH-FLACの特徴的な組織形態や臨床病理学的特徴に寄与している可能性が考えられる．また，これまでCTNNB1変異やβ-cateninの異常集積はL-FLACの特徴とされてきたが，これらの所見はH-FLACにおいても低頻度にみられることが明らかとなった．