| Project/Area Number |
16K09318
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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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| Research Field |
Gastroenterology
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| Research Institution | Yokohama City University |
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Principal Investigator |
Sakai Eiji 横浜市立大学, 医学研究科, 客員研究員 (30600233)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 大腸発癌 / 遺伝子変異 / 鋸歯状腺腫 / 大腸癌 / 遺伝子解析 / 大腸腺腫 |
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| Outline of Final Research Achievements |
We previously revealed that LST showed high frequency of APC mutation even at adenoma stage, suggesting its involvement in initiation stage of LST, like adenoma-carcinoma sequence. TP53 mutation was never detected by adenoma stage, but specifically detected in cancer samples in both LST-G and LST-NG, suggesting its involvement in cancer development from adenoma. In the present study, we also confirmed TP53 can be key driver gene which initiates protruded adenoma into intramucosal carcinoma. On the other hand, mutation of MLH family was suspected to associate with initiation sessile serrated adenoma (SSA/P) to that with cytological dysplasia. However the lower amount of DNA samples obtained by cancerous lesions both the protruded adenocarcinoma and SSA/P with cytological dysplasia, we need to obtain additional samples, thus the present study is currently in progress.
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| Academic Significance and Societal Importance of the Research Achievements |
これまではTP53が腺腫から癌への進展で重要な働きを担うとされてきたが、すべての発癌経路で同様とは考えにくく、経路ごとの相違は興味深い。したがって、本研究は基礎研究として大腸発癌機構の解明につながる重要なものである。さらに、早期癌に特異的な遺伝子異常を捉えることは、大腸癌の早期発見につながる可能性があり、臨床的にも極めて重要である。特にSSA/PやLST-NGはその形態から内視鏡的に見逃されることも多い。近年、血液中を循環する微量な癌細胞由来DNAから遺伝子異常を拾い上げる試みがなされており、本研究で同定した遺伝子異常をターゲットに早期発見のためのキットを作成することが可能かもしれない。
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