2023 Fiscal Year Final Research Report
Can oncogenic mutations detected in normal endometrial epithelium be drivers for endometrial regeneration or cancer development?
Project/Area Number |
21H03077
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Shimane University |
Principal Investigator |
Kyo Satoru 島根大学, 学術研究院医学・看護学系, 教授 (50272969)
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Project Period (FY) |
2021-04-01 – 2024-03-31
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Keywords | 正常子宮内膜 / 癌遺伝子 / KRAS / PIK3CA |
Outline of Final Research Achievements |
In order to clarify the biological significance of cancer gene mutations present in normal endometrium, we collected normal endometrium from uterus removed due to benign disease, and cancer gene mutations were analyzed by sequencing of isolated single glandular ducts. In addition, single gland ducts were subjected to spheroid culture, followed by sequencing of spheroids that grew to a diameter of 2 mm or more. PIK3CA or KRAS gene mutations were found in 9.3% of the glandular ducts. Analysis of 33 spheroids revealed mutations in 22 spheroids, and all of the gene mutations observed were in PIK3CA.
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Free Research Field |
婦人科腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
正常子宮内膜にも一定の頻度で癌遺伝子変異が入っていること、PIK3CAがspheroid形成に重要な役割を担っていることが明らかとなった。spheroidはstem-richな集団と考えられるため、正常内膜では、内膜stem cellへのPIK3CA遺伝子変異が入っている可能性が示唆され、閉経期までに渡り旺盛な再生増殖を示す内膜のbiologyや癌化過程の一翼を担っている能性がある。これらの結果は、臨床的には月経や着床という子宮内膜の生理的な異常や疾患との関連性を探求する研究に応用したり、変異と内膜癌化の関連性を探究することで、発がんリスクのスクリーニングに役立てる研究にも繋がる可能性がある。
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