| Project/Area Number |
16K09304
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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 | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山本 英一郎 札幌医科大学, 医学部, 講師 (60567915)
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| Research Collaborator |
Suzuki Hiromu 札幌医科大学, 分子生物学講座, 教授 (20381254)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 大腸癌 / 大腸鋸歯状腺腫 / 遺伝子メチル化 / 遺伝子変異 / Wntシグナル経路 |
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| Outline of Final Research Achievements |
To clarify the molecular and clinicopathological characteristics of colorectal serrated lesions, we examined the mutation and methylation of cancer-associated genes in 78 serrated lesions, including traditional serrated adenomas (TSAs) and sessile serrated adenomas (SSAs). The prevalence of mutations in genes associated with Wnt signaling pathway was significantly higher in TSAs than SSAs. In addition, SMOC1 methylation was detected in 54.1% of TSAs but in no SSAs. These results suggests the presence of distinct carcinogenic pathways of TSAs from other precursor lesions. Furthermore, we detected significant differences in clinicopathological and molecular variables between TSAs with KRAS or BRAF mutation, which may indicate the presence of separate carcinogenic pathways among TSAs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、従来より想定されてきた大腸鋸歯状腺腫（TSA）を前癌病変とする発癌経路の存在が示された。また、他の鋸歯状病変と比較してWntシグナル経路の異常が大きく関与していることが明らかとなった。今後、大腸鋸歯状病変の進展・発育により形成されると考えられている高悪性度大腸癌と分子プロファイルを比較することにより、TSAから高悪性度大腸癌に至る新たな発癌経路が確立できる。また、予後不良の高悪性度大腸癌に対する分子標的治療の開発に応用できる。
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