| Project/Area Number |
20K17641
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Takane Kiyoko 東京大学, 医科学研究所, 助教 (60756112)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 腹膜偽粘液腫 / DNAメチル化 / KRAS / GNAS / オルガノイド / 腹膜偽粘液種 / 大腸癌 |
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| Outline of Research at the Start |
腹膜偽粘液腫は、腫瘍細胞から分泌されるゼラチン様物質が腹腔内に貯留し、腹部膨満や腹痛などの様々な症状を呈する。100万人に1-2人の稀な疾患であり、5年生存率が30％～50％と報告されているが、患者の大多数は再発を繰り返し、複数回の手術の実施など、患者のQOLは必ずしも高くない。そこで本申請課題では、腹膜偽粘液腫の発生・進展に関わる遺伝子変化を明らかにし、その治療標的遺伝候補を同定する。
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| Outline of Final Research Achievements |
Pseudomyxoma peritonei (PMP) is a disease characterized by progressive accumulation of intraperitoneal mucinous ascites caused by neoplasms in the abdominal cavity. Although the advancement in surgical treatment with intraoperative chemotherapy has improved the survival of patients with PMP, most of the patients need repeated treatment, which is lowering their quality of life. Therefore, the development of effective therapeutic drug(s) is a matter of pressing concern. Genetic analyses and expression profile analyses of PMP have clarified the frequent activation of GNAS and/or KRAS. However, the involvement of global epigenetic alterations in PMPs has not been reported. In this study, we performed genome-wide DNA methylation analysis using 15 appendiceal PMP samples. As a result, we clarified that the 15 PMPs are classified into at least two epigenotypes, unique methylation epigenotype (UME) and normal-like methylation epigenotype (NLME).
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| Academic Significance and Societal Importance of the Research Achievements |
PMPは稀な腫瘍であるが、比較的早期に腫瘍が進展し、広範な腹膜転移をきたす。膵臓の乳管内乳頭粘液性腫瘍(IPMN)も、高頻度にKRASおよびGNASの変異が認められ、PMPと共通した機序で腫瘍が発生または進展している可能性が高い。このことは、PMPの発がんメカニズム解明と、新たなバイオマーカー、治療標的分子の探索により、がんの転移の抑制や、IPMNや腹膜播種などの治療に役立つ可能性があることを意味している。
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