| Project/Area Number |
20K07382
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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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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Hashimoto Taiki 国立研究開発法人国立がん研究センター, 中央病院, 医員 (40773875)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 大腸癌 / WNT / R-spondin / RSPO / 鋸歯状病変 |
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| Outline of Research at the Start |
大腸癌の新鮮凍結組織からのRSPO融合陽性例の同定、およびホルマリン固定パラフィン包埋(FFPE)標本からのRSPO融合検出法の確立を行い、 RSPO融合陽性大腸癌の臨床病理学的特徴の解明を目指す。
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| Outline of Final Research Achievements |
We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription-PCR, and subjected RSPO fusion-positive tumors to whole-exome sequencing (WES). Of the 1019 CRCs, 29 (2.8%) were found to harbor RSPO fusions, consisting of five with an EIF3E-RSPO2 fusion and 24 with PTPRK-RSPO3 fusions. Patients included 17 women and 12 men, and 13 tumors (45%) were right-sided. Half of the tumors (13/29, 45%) had a focal or extensive mucinous component, which was significantly more frequent than in RSPO fusion-negative tumors (13%; P = 8.1 × 10－7). WES identified KRAS, BRAF, and NRAS mutations in 27 tumors (93%). However, pathogenic mutations in major WNT pathway genes, such as APC, CTNNB1, and RNF43, were absent. Although RSPO fusion status did not significantly influence overall or recurrence-free survival. A pooled analysis of previous studies confirmed these clinicopathological and genetic features.
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| Academic Significance and Societal Importance of the Research Achievements |
R-spondin標的薬剤の臨床応用にあたっては、病理検体を用いてRSPO融合陽性例を同定し、適応となる患者を見つけ出す必要があるが、本研究によりRSPO融合陽性大腸癌の臨床病理学的・分子生物学的特徴が明らかになった。今後、効率的なRSPO融合の検出法の確立が期待される。
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