全基因组和外显子组测序在肝癌研究中的应用进展

摘要

Hepatocellular carcinoma (HCC) is one of the most common cancers world-wide.Known risk factors and prognostic factors of the disease include virus infection of hepatitis B and hepatitis C,alcohol intake,carcinogenic substances such as aflatoxin B1.So far,multiple studies have identified the molecular genetic characteristics of the tumor utilizing nextgeneration sequencing technologies.The whole-genome and exome sequencing of HCC can help to find potential key oncogenes and tumor suppressor genes,as well as improving molecular diagnosis of HCC,which can help to find new therapeutic targets and determine prognosis.In 2011,The US researchers whole-genome sequencing (2 patients,with HBV and HCV infection,respectively),whole genome exome sequencing (47 patients,of which 33 with HCV infection,7 with HBV infection,and 7 with non-viral infection),Sanger sequencing (94 patients,of which 52 with HBV infection,36 with HCV infection,and 6 with non-viral infection),gene expression (4 patients,of which 2 with HBV infection and 2 with HCV infection),and Epigenetic inheritance (1 case,with HCV infection),as well as other research strategies in search of treatment approaches for liver cancer from genomics perspectives,in hope of improving long-term survival rate of patients with HCC[1].This review summarizes the HCC-related predisposing genes from whole-genome and exome studies with next generation sequencing technologies.%肝细胞癌(HCC)是世界最常见的癌症之一.已知HCC有多个危险因素,包括慢性乙肝病毒和丙肝病毒感染、酒精摄入、致癌物质如黄曲霉毒素B1等,均参与肝癌的发生、发展.目前,已有多项研究利用新一代测序技术确定了肿瘤的分子遗传学特征.利用全基因组和外显子组测序对HCC进行研究,有助于寻找潜在关键的癌基因及抑癌基因,为HCC的分子诊断提供参考,有助于寻找新的治疗靶点及判断预后.2011年,美国研究人员计划通过全基因组测序(2例患者,HBV和HCV感染各1例)、全基因组外显子组测序(47例患者,33例为HCV感染、7例为HBV感染、7例为非病毒感染)、Sanger测序(94例患者,52例为HBV感染、36例为HCV感染、6例为非病毒感染)、基因表达(4例患者,HBV和HCV感染各2例)和表观遗传(1例患者,为HCV感染)等研究策略从基因组学方面寻找肝癌的治疗手段,期望改善HCC患者长期生存率[1].本文就新一代测序技术在全基因组和外显子组范围内搜寻HCC相关易感基因研究作一综述.