2022 Fiscal Year Final Research Report
Analysis of the carcinogenesis with GAPPS patients
| Project/Area Number |
21K15551
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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 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | GAPPS / 発癌機序 / オルガノイド |
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| Outline of Final Research Achievements |
We included 7 GAPPS families (16 patients) in the analysis. Median age was 43.5 (18-84) years old and male was 7. 8 patients had gastric cancer (stage I/II/IV=3:1:4). Germline analysis of the APC gene were performed with direct-sequencing method, and thus 14 patients had the point mutation of APC exon 1B. Genomic carcinogenesis analysis with biopsy specimen of normal mucosa, dysplasia and adenocarcinoma demonstrated that the gene A, B and C were associated with carcinogenesis of GAPPS patients. In particular, gene A was variously muted in each specimen, therefore that revealed the relation to carcinogenesis. On the other hand, chromosomal analysis demonstrated that chromosomal abnormality was also associated with carcinogenesis. Organoids were established with the particular growth factors.
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| Free Research Field |
消化器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
GAPPSの病態および臨床指針は全世界的に未確立であり，その発癌機序の解明は治療方針の策定において重要な貢献をもたらす．遺伝子プロファイリングの解析により発癌に関与するドライバー遺伝子の候補が挙がり，これに基づいた治療薬開発につながるものと考えられる．また，発癌機序が多彩であることが判明しており，GAPPS関連胃癌における予後不良因子である可能性がある．染色体異常に関しては未報告であり，今後の核酸医薬品や遺伝子関連治療薬の開発にも重要な知見をもたらした．GAPPSは希少疾患ゆえ，病態解析を行うことが困難とされているが，オルガノイド樹立により候補薬剤ごとの網羅的解析を十分に行うことが期待される．
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