Genomic heterogeneity in hepatocellular carcinoma from a cancer stem cell perspective.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyoto University
• Principal Investigator: Ishii Takamichi 京都大学, 医学研究科, 講師 (70456789)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 混合型肝癌 / 細胆管細胞癌 / 癌幹細胞 / ゲノム解析

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.

Free Research Field

消化器外科学

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．