| Project/Area Number |
19K09145
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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 55020:Digestive surgery-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
河合 隆之 京都大学, 医学研究科, 客員研究員 (00813867)
小木曾 聡 京都大学, 医学研究科, 助教 (10804734)
上本 伸二 滋賀医科大学, 医学部, 学長 (40252449)
福光 剣 京都大学, 医学研究科, 特定講師 (70700516)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 混合型肝癌 / 細胆管細胞癌 / 癌幹細胞 / ゲノム解析 / 肝癌 / ゲノム / ゲノムシークエンス / 胆管癌 / 肝細胞癌 / ゲノム不均一性 / K19陽性肝細胞癌 |
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| Outline of Research at the Start |
本研究では，目的達成のため以下の2項目について研究を行う．
1. K19陽性肝細胞癌とK19陰性肝細胞癌と間で全ゲノムシークエンスを比較することによる腫瘍間不均一性の解明
2. 古典的混合型肝癌において肝細胞癌成分と胆管癌成分とからDNAを抽出しゲノムシークエンスを比較することによる腫瘍内不均一性の実態把握
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| Outline of Final Research Achievements |
The majority of primary liver cancers are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), but there are subclasses with characteristics intermediate between the two. There are two subtypes of hepatocarcinoma with intermediate characteristics between HCC and iCCA: combined hepatocellular-cholangiocarcinoma (cHCC-CCA), which have both HCC and CCA components in the same tumor, and cholangiolocellular carcinoma (CLC), which resemble the small bile ducts. The aim of this study was to investigate the clinicopathological characteristics of these tumors with intermediate characteristics and to analyze their genomes using next-generation sequencers.
The small-sized cHCC-CCL tumors were TP53 mutation-positive and showed a pattern similar to HCC, whereas the CLC tumors resembled CCA. On the other hand, CLC had a gene mutation pattern similar to that of CCA, and some cases recurred clinically as iCCA.
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| Academic Significance and Societal Importance of the Research Achievements |
稀な腫瘍型であるcHCC-CCAとCLCのゲノム解析を行い，原発性肝癌でも多くを占めるHCCやiCCAと比較検討した．
cHCC-CCAで分類されていたカテゴリーはTP53変異の有無によってさらに分類され，TP53変異のある症例は小型でHCCとよく似た性質を有していた．一方，CLCはiCCAとよく似た特徴を示していた．
これらの結果からはHCCやiCCAとの類似性，相違性が判明し，稀な腫瘍型ではあるが遺伝子変異のパターンによってはHCCやiCCAに準じた治療法が有効である可能性が示唆された．
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