The elucidation of pathophysiology and the development of adenomyosis by selective tissue sampling and integrated genomic analysis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18633
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Niigata University
• Principal Investigator: Suda Kazuaki 新潟大学, 医歯学総合研究科, 客員研究員 (80650621)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 子宮腺筋症 / ゲノム / レーザーマイクロダイセクション

Outline of Final Research Achievements

Multi-sampling was performed from surgically removed uteruses of a total of 23 patients with gynecological disease. Tissue-specific sampling by laser microdissection was performed on 44 samples of adenomyotic epithelial tissue, 13 samples of adenomyotic stromal tissue, and 57 samples of normal endometrial tissue. The target sequence was performed using a target probe of 76 genes. The most common genes with mutations in adenomyotic epithelial tissue were KRAS, ARID1A, ARHGAP35, and PIK3CA. KRAS mutations were shared between adenomyosis and the normal endometrium in 3 cases. Combined with the data from the previous study, the results showed that KRAS and PIK3CA mutations were found more frequently in the endometrium coexisting with adenomyosis than that without adenomyosis.

Free Research Field

産婦人科ゲノム

Academic Significance and Societal Importance of the Research Achievements

子宮腺筋症組織に対しターゲットシーケンスを行い、遺伝子プロファイルを明らかにした。徹底した組織選択的採取により腺筋症上皮はモノクローナルであり、腺筋症間質は不均一な細胞集団であることを解明し、両者の発生起源は異なる可能性を示唆した。また腺筋症と共存する正常子宮内膜上皮は、KRASやPIK3CAといった子宮内膜癌でも認められる癌遺伝子変異の存在頻度が高いことを明らかにし、これは子宮内膜関連疾患の病態解明にも寄与する結果であるといえる。