2021 Fiscal Year Final Research Report
Establishment of effective and reliable detection system for genomic alterations in uterine adenomyosis
| Project/Area Number |
19K07708
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Aichi Cancer Center Research Institute (2021)
National Cancer Center Japan (2019-2020) |
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Principal Investigator |
Inoue Satoshi 愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, ユニット長 (30801930)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 子宮腺筋症 / 子宮内膜症 / 子宮内膜 / ゲノム解析 |
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| Outline of Final Research Achievements |
Uterine adenomyosis is a benign disorder that often co-occurs with endometriosis and/or leiomyoma and impairs quality-of-life. In contrast to endometriosis and leiomyoma, the genomic features of adenomyosis are unknown. Our NGS analyses of adenomyosis revealed that recurrent oncogenic KRAS mutations were detected in 37% adenomyosis. Multi-regional sequencings showed that adenomyosis is an oligoclonal disease, with some mutations also detected in adjacent normal endometrium and/or co-occurring endometriosis. KRAS mutations were significantly more frequent in adenomyosis with co-occurring endometriosis, who had been pretreated with a progestin, or low PR experssion. Our first genetic characterization of adenomyosis suggest a common molecular etiology of adenomyotic and endometriotic clones, potentially explaining the frequent co-occurrence. Our findings may point towards genetically-guided precision therapy and/or relapse risk assessment after uterine sparing surgery.
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| Free Research Field |
ゲノム解析
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、子宮腺筋症のゲノム異常を世界で初めて明らかにした。その結果、子宮腺筋症という疾患は、子宮内膜症と同様に正所性子宮内膜において共通の起源となるクローンを有することが明らかとなり、両疾患が高頻度に併発するという臨床上の特徴を分子レベルで説明することが出来た。さらにKRAS変異クローンは、プロゲステロン受容体発現抑制を起こし、実臨床で用いられているプロゲスチン抵抗性を獲得している可能性を示唆した。本研究は、ゲノム解析というアプロ―チにより、子宮内膜症と腺筋症との関係を分子レベルで明らかにしただけでなく、個別化医療の対象となりうる疾患であることを明らかにした点が本研究成果の意義と思われる。
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