转座子诱变鉴定出慢性乙型肝炎小鼠模型中驱动肝细胞癌的基因。
Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model.
机构信息
Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
出版信息
Nat Genet. 2014 Jan;46(1):24-32. doi: 10.1038/ng.2847. Epub 2013 Dec 8.
Abstract
The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC.
摘要
导致肝细胞癌 (HCC) 的最常见风险因素是慢性乙型肝炎病毒 (HBV) 感染。为了更好地了解驱动 HCC 的进化力量，我们在小鼠 HBV HCC 模型中进行了近乎饱和的转座子诱变筛选。该筛选鉴定出 21 个候选早期驱动基因和大量（2860 个）候选晚期驱动基因，这些基因富集了在人类 HCC 中发生突变、失调或在信号通路中发挥作用的基因，其中有 1199 个基因与细胞代谢过程有关。我们的研究提供了 HCC 遗传景观的全面概述。
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