Genetic Alterations and Oncogenic Pathways in Hepatocellular Carcinoma
Genetic Alterations and Oncogenic Pathways in Hepatocellular Carcinoma
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DOI：
10.1111/j.1749-6632.2002.tb04091.x
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发表时间：
2002-06
影响因子：
5.2
通讯作者：
Laurence Levy;C. Renard;Yu Wei;M. Buendia
中科院分区：
文献类型：
--
作者：
Laurence Levy;C. Renard;Yu Wei;M. Buendia
摘要：肝细胞癌（HCC）是原发性肝癌的一种主要类型，也是与病毒因素病因相关的罕见人类肿瘤之一。慢性感染B型肝炎病毒（HBV）和丙型肝炎病毒（HCV）已牵连在全球约80%的情况下，和其他已知的环境风险因素，包括酗酒和黄曲霉毒素B1的饮食摄入，可能与病毒感染协同作用。通过全基因组等位基因型研究和分子细胞遗传学分析发现的主要遗传异常，提供了对导致HCC发展的分子机制的最新见解。此外，几种致癌途径与肝细胞的恶性转化有关。在大约30%的HCC病例中，p53肿瘤抑制基因的突变和等位基因缺失导致的失活主要与暴露于黄曲霉毒素B1和HBV感染相关。相比之下，约22%的HCC中的β连环蛋白基因突变在HBV相关肿瘤中更为罕见。细胞周期蛋白D1的激活和Rb通路的破坏也通常参与肝脏肿瘤的发生。新的主要挑战包括鉴定位于频繁改变的染色体区域的候选基因以及由不同风险因素驱动的致癌途径。这一研究可能有助于阐明HBV和HCV的致瘤作用。它也可能允许准确评估预后和治疗干预的主要目标。
Abstract: Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been implicated in about 80% of cases worldwide, and other known environmental risk factors, including alcohol abuse and dietary intake of aflatoxin B1, might synergize with viral infections. Recent insight into the molecular mechanisms leading to HCC development has been provided by the identification of major genetic abnormalities revealed by genomewide allelotype studies and molecular cytogenetic analysis. Moreover, several oncogenic pathways have been implicated in malignant transformation of liver cells. Inactivation of the p53 tumor suppressor gene by mutations and allelic deletions in about 30% of HCC cases has been associated predominantly with exposure to aflatoxin B1 and HBV infection. By contrast, a mutation in the β‐catenin gene in around 22% of HCCs is more rare in HBV‐associated tumors. Activation of cyclin D1 and disruption of the Rb pathway are also commonly involved in liver tumorigenesis. New major challenges include the identification of candidate genes located in frequently altered chromosomal regions and that of oncogenic pathways driven by different risk factors. This search might shed some light on the tumorigenic role of HBV and HCV. It might also permit accurate evaluation of major targets for prognostic and therapeutic intervention.