Institute of Liver Diseases, Huai'an Fourth People's Hospital, Huai'an, Jiangsu 223002, P.R. China.
Oncol Rep. 2013 Oct;30(4):1906-12. doi: 10.3892/or.2013.2652. Epub 2013 Aug 2.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third primary cause of cancer-related mortality worldwide. The molecular mechanisms underlying the initiation and formation of HCC remain obscure. In the present study, we performed exome sequencing using tumor and normal tissues from 3 hepatitis B virus (HBV)-positive BCLC stage A HCC patients. Bioinformatic analysis was performed to find candidate protein-altering somatic mutations. Eighty damaging mutations were validated and 59 genes were reported to be mutated in HBV-related HCCs for the first time here. Further analysis using whole genome sequencing (WGS) data of 88 HBV-related HCC patients from the European Genome-phenome Archive database showed that mutations in 33 of the 59 genes were also detected in other samples. Variants of two newly found genes, ZNF717 and PARP4, were detected in more than 10% of the WGS samples. Several other genes, such as FLNA and CNTN2, are also noteworthy. Thus, the exome sequencing analysis of three BCLC stage A patients provides new insights into the molecular events governing the early steps of HBV-induced HCC tumorigenesis.
肝细胞癌（HCC）是最常见的肝癌类型，是全球癌症相关死亡的第三大主要原因。HCC 发生和形成的分子机制仍不清楚。在本研究中，我们对 3 例乙型肝炎病毒（HBV）阳性 BCLC 分期 A HCC 患者的肿瘤和正常组织进行了外显子组测序。通过生物信息学分析寻找候选蛋白改变的体细胞突变。验证了 80 个破坏性突变，并首次报道了 59 个在 HBV 相关 HCC 中发生突变的基因。进一步使用欧洲基因组-表型档案数据库中 88 例 HBV 相关 HCC 患者的全基因组测序（WGS）数据进行分析，结果显示在其他样本中也检测到了 33 个 59 个基因中的突变。两个新发现基因 ZNF717 和 PARP4 的变体在超过 10%的 WGS 样本中被检测到。其他一些基因，如 FLNA 和 CNTN2，也值得注意。因此，对 3 例 BCLC 分期 A 患者的外显子组测序分析为 HBV 诱导 HCC 肿瘤发生的早期步骤提供了对分子事件的新见解。
