Epigenomic regulation during development of testicular germ cell tumor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Keio University
• Principal Investigator: Arai Eri 慶應義塾大学, 医学部(信濃町), 准教授 (40446547)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 精巣腫瘍 / 精巣胚細胞腫瘍 / セミノーマ / 胎児性癌 / DNAメチル化 / エピジェネティクス / エピゲノム / 分化調節

Outline of Final Research Achievements

Testicular germ cell tumors (TCGTs) are malignant tumors which show intratumoral differentiation mimicking normal development. Each histologic subtype of TGCT had a unique DNA methylation profile, and their DNA methylation profiles were followed a differentiation process. Seminomas were clearly divided into two groups: Sem2, whose DNA methylation profile resembled embryonal carcinoma, and Sem1, whose did not. DNA hypermethylation occurred significantly in regions critical for the maintenance of chromosomal stability in Sem2 compared to Sem1. Genes that show different DNA methylation changes in the two groups of seminomas and that may result in different expression may be useful in diagnosing tumor grade and predicting prognosis of seminoma.

Free Research Field

分子病理学

Academic Significance and Societal Importance of the Research Achievements

精巣胚細胞腫瘍は希少がんかつAYA世代に発生するがんである。形態学を基盤とした着想と技術に基づき、精巣胚細胞腫瘍がエピジェネティックに正常発生分化を模倣すること、形態学的に見分けのつかないセミノーマが悪性度の異なる2群に分けられることを明らかにした。これにより、最も頻度の高い精巣胚細胞腫瘍であるセミノーマの悪性度診断や予後予測、精巣胚細胞腫瘍の分化誘導療法の可能性を提示した。