Human Genome Center of Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Nat Genet. 2012 Oct;44(10):1117-21. doi: 10.1038/ng.2391. Epub 2012 Aug 26.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.
肝细胞癌 (HCC) 是全球最常见的癌症之一，具有转移和浸润邻近及更远组织的倾向。HCC 与多种风险因素相关，包括乙型肝炎病毒 (HBV) 感染，在中国尤为普遍。在这里，我们使用外显子组测序鉴定了 10 名 HBV 阳性 HCC 伴门静脉癌栓 (PVTT) 、肝内转移患者的体细胞突变。在 331 个非沉默突变中，经常发现 C:G>A:T 和 T:A>A:T 颠换。值得注意的是，编码 SWI/SNF 染色质重塑复合物组成部分的 ARID1A 在 110 例 (13%) HBV 相关 HCC 标本中发生突变。我们使用 RNA 干扰来评估 91 个已确认突变基因在细胞存活中的作用。结果表明，其中 7 个基因，包括 VCAM1 和 CDK14，可能赋予 HCC 细胞生长和浸润能力。这项研究提供了一个可能与晚期 HCC 相关的体细胞突变全景。
