2021 Fiscal Year Final Research Report
Comprehensive genetic analysis of the colorectal serrated neoplasia pathway
Project/Area Number |
18K15796
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Juntendo University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Keywords | serrated pathway / 大腸鋸歯状病変 / 大腸癌発育進展 / serrated lesion / sessile serrated lesion |
Outline of Final Research Achievements |
Lost MLH1 expression was found in 5 cases. All lesions studied were positive for nuclear β-catenin expression. Regarding phenotypic mucin expression, all lesions were positive for MUC2, but negative for CD10. MUC5AC and MUC6 positivity was observed in 7 cases. Genetically, the most frequently mutated gene was BRAF (7 cases), and other mutations were detected in FBXW7 (3 cases); TP53 (2 cases), and KIT, PTEN, SMAD4, and SMARCB1 (1 case each). Furthermore, 4 of 8 lesions were MSI-high and the remaining 4 lesions were microsatellite-stable (MSS). Interestingly, all 4 MSI-high lesions displayed MLH1 loss, 3 of which harbored a FBXW7 mutation, but not a TP53 mutation. However, 2 MSS lesions harbored a TP53 mutation, although none harbored a FBXW7 mutation.
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Free Research Field |
大腸鋸歯状病変
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Academic Significance and Societal Importance of the Research Achievements |
serrated neoplasia pathwayはその発育進展にBRAF変異、Wnt/β-cateninシグナルの活性化、胃腸混合型粘液形質が関与すると考えられた。さらにserrated neoplasia pathwayはMSI大腸癌へと進展する経路のみならずMSS大腸癌へと進展する2つの経路が存在し、前者ではMLH1発現低下やFBXW7変異、後者ではTP53変異が関与するなど異なる分子生物学的特徴を有する可能性が示唆された。BRAF変異MSS大腸癌は組織学的に悪性度の高い病変として知られており、serrated neoplasia pathwayのさらなる解析が望まれる。
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