2023 Fiscal Year Final Research Report
The role of fusion genes in multistep progression of cancer
| Project/Area Number |
19K07430
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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 | Aichi Cancer Center Research Institute |
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Principal Investigator |
Hosoda Waki 愛知県がんセンター(研究所), がん情報・対策研究分野, 研究員 (00728412)
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| Co-Investigator(Kenkyū-buntansha) |
谷田部 恭 国立研究開発法人国立がん研究センター, 中央病院, 科長 (90280809)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | Pancreatic cancer / tumorigenesis / KRAS mutation / fusion gene |
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| Outline of Final Research Achievements |
We studied clinicopathological characteristics of seventy five pancreatic ductal adenocarcinoma (PDAC) with wild-type KRAS and their genetic alterations including gene fusion as well as somatic mutation. Furthermore, we investigated precursor lesions of PDAC that were located adjacent to the PDAC and their molecular alterations to discuss the potential role of fusions in the formation of PDAC. Using next-generation sequencing, we showed that fusion genes were involved in KRAS wild-type PDAC, some of which (ALK, FGFR2) were known to be correlated with sensitivity to molecular targeted drugs in other types of cancer. Notably, we identified five PDAC cases that were associated with high-grade precursor lesions and showed that two precursor lesions were positive for fusions identical to those detected in invasive carcinomas. These results indicate, for the first time, that gene fusion plays an important role in the formation of PDAC with wild-type KRAS.
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| Free Research Field |
Pancreatic cancer research
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| Academic Significance and Societal Importance of the Research Achievements |
膵管癌のKRAS遺伝子変異の検討によるKRAS変異陰性型の膵管癌の抽出は、何らかの特徴的な分子異常を有し、特に治療に紐づく融合遺伝子を有する頻度が高いことが明らかとなった。
KRAS変異陰性型膵癌に特徴的な臨床的特徴は見出せなかったが、病理学的には非通常型の組織型がみられるという特徴が明らかとなり、今後このような組織型の膵癌も遺伝子変異のみならず融合遺伝子も検索することで、より効率的に治療に紐づく分子異常を検出できる可能性があることが示唆された。病理学的にはこれら融合遺伝子が腫瘍発生の前駆病変の段階からみられることが明らかとなり、融合遺伝子が腫瘍発生の重要なドライバーとなりうることが示された。
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