2022 Fiscal Year Final Research Report
Molecular characterization of normal endometrial epithelial cells with cancer-associated gene mutations
Project/Area Number |
20K07318
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 48040:Medical biochemistry-related
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Research Institution | Sasaki Foundation |
Principal Investigator |
Nakaoka Hirofumi 公益財団法人佐々木研究所, 附属研究所, 部長 (70611193)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 子宮内膜 / 癌関連遺伝子 / 体細胞変異 / クローン性増殖 / ゲノム解析 / トランスクリプトーム解析 |
Outline of Final Research Achievements |
We showed that somatic mutations in cancer-associated genes accumulated in the human normal endometrial epithelium. Endometrial glands with cancer-associated gene mutations spatially expanded in the substantial areas of the endometrium. By using three-dimensional imaging analysis, we discovered the plexus network-like glandular structure at the bottom of the endometrium ran horizontally along the muscular layer, and several branches rose from the structure toward the luminal epithelium. Moreover, mutant clones detected in the vertical glands diversify by acquiring additional mutations. These results suggest that clonal expansions through the network-like structures are involved in the mechanism by which mutant clones extend their territories. By extracting both DNA and RNA, we conducted transcriptome analysis for the single endometrial glands whose mutation profiles and spatial information were available.
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Free Research Field |
ゲノム医科学
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Academic Significance and Societal Importance of the Research Achievements |
月経による子宮内膜の組織再生を繰り返す過程において、一見正常な子宮内膜において癌関連遺伝子の体細胞変異を有する上皮細胞が蓄積していくことが分かった。三次元イメージング解析とゲノム解析によって、癌関連遺伝子に変異を有する上皮細胞が空間的に増殖するメカニズムを明らかにした。癌関連遺伝子に体細胞変異を有し、空間的に増殖する上皮細胞の特徴を明らかにするため、網羅的遺伝子発現解析を行った。子宮内膜症、子宮腺筋症、子宮体癌や卵巣癌といった子宮内膜組織に関連する疾患の発症機序を理解するための重要な知見が得られた。
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