Chronic liver disease and primary liver cancer are a massive global problem, with a future increase in incidences predicted. The most prevalent form of primary liver cancer, Hepatocellular carcinoma (HCC), occurs after years of chronic liver disease. Mutations in the genome are a causative and defining feature of all cancers. Chronic liver disease, mostly at the cirrhotic stage, causes the accumulation of progressive mutations which can drive cancer development. Within the liver a Darwinian process selects out dominant clones with selected driver mutations but also leaves a trail of passenger mutations which can be followed allowing tracking of this evolution. Understanding what causes specific mutations and how they combine with one another to form cancer is a question at the heart of understanding, preventing and tackling liver cancer. Here we review the landscape of gene mutations in cirrhosis, especially those paving the path toward HCC development characterised by recent studies capitalising on technological advances in genomic sequencing. With these insights we are beginning to understand how cancers form in the liver, particularly on the background of chronic liver disease. This knowledge may soon lead to breakthroughs in the way we detect, diagnose and treat this devastating disease.

中文翻译：

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肝硬化和肝细胞癌的基因突变概况

慢性肝病和原发性肝癌是一个巨大的全球性问题，预计未来发病率会增加。原发性肝癌最普遍的形式是肝细胞癌 (HCC)，发生在多年慢性肝病之后。基因组中的突变是所有癌症的致病和决定性特征。慢性肝病，主要是在肝硬化阶段，会导致进行性突变的积累，从而推动癌症的发展。在肝脏内，达尔文过程会选择具有选定驱动突变的显性克隆，但也会留下一系列乘客突变，可以跟踪这些突变，从而跟踪这种进化。了解导致特定突变的原因以及它们如何相互结合形成癌症是了解、预防和应对肝癌的核心问题。在这里，我们回顾了肝硬化中基因突变的前景，特别是那些为 HCC 发展铺平道路的突变，这些突变以最近利用基因组测序技术进步的研究为特征。有了这些见解，我们开始了解癌症是如何在肝脏中形成的，尤其是在慢性肝病的背景下。这些知识可能很快会导致我们检测、诊断和治疗这种毁灭性疾病的方式取得突破。