PreS2 Mutant of Hepatitis B Virus as Early Marker of Hepatocellular Carcinoma

描述（由申请人提供）：乙型肝炎病毒（HBV）是全球和美国严重肝脏疾病的主要原因，包括慢性肝炎，肝硬化和肝细胞癌（HCC），特别是少数民族，如非洲裔美国人，美洲原住民和亚裔美国人。最近的临床数据表明，HCC和HBV突变体与表面基因preS2区域的框架内缺失有关。我们假设preS2突变HBV基因组在HBV相关癌变中起因果作用，因此这些突变体在患者中的出现可作为HCC风险的早期标志物。我们将通过确认preS2突变体与HCC之间的流行病学联系来验证这一假设，并确定这些突变体的存在是否可以作为慢性乙型肝炎患者HCC发展风险增加的标志。预计这些实验将为preS2突变体作为慢性乙型肝炎HCC风险标志的可能用途提供直接证据。以及在未来发现预防和/或治疗HCC的分子靶点。乙型肝炎病毒是世界上造成痛苦和死亡的一个主要原因，它会导致肝损伤、肝硬化（肝瘢痕），最重要的是，会导致肝癌。目前对肝癌的治疗是不充分的，很大程度上是因为我们不能足够早地发现癌症。我们希望我们的研究能够为这些患者的早期发现和治疗肝癌提供新的方法。

DESCRIPTION (provided by applicant): Hepatitis B virus (HBV) is a major cause of serious liver diseases, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) throughout the world and the US, especially among minorities such as African Americans, Native Americans, and Asian Americans. Recent clinical data have pointed to an association between HCC and HBV mutants with in-frame deletions in the preS2 region of the surface gene. We hypothesize that preS2 mutant HBV genomes play a causal role in HBV-associated carcinogenesis, and hence the appearance of these mutants in patients can be used as an early marker for risk of HCC. We will test this hypothesis, by confirming an epidemiological link between preS2 mutants and HCC, and determining if the presence of these mutants can be used as a marker for increased risk of HCC development in patients with chronic hepatitis B. It is anticipated that these experiments will provide direct evidence on the possible utility of preS2 mutants as a marker of HCC risk in chronic hepatitis B, as well as lead in the future to the identification of molecular targets for the prevention and/or therapy of HCC. Hepatitis B virus is a major cause of suffering and death in the world, by causing liver injury, cirrhosis (liver scarring) and, most importantly, liver cancer. Current treatment for liver cancer is inadequate, to a large extent because of our inability to detect the cancer early enough. We hope that our research can lead to the development of new ways for the early detection and hence treatment of liver cancer in these patients.