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

描述（申请人提供）：B肝炎病毒（HBV）是世界各地和美国严重肝脏疾病（包括慢性肝炎、肝硬化和肝细胞癌（HCC））的主要原因，尤其是在非裔美国人、美洲原住民等少数族裔中。和亚裔美国人。最近的临床数据指出，HCC和HBV突变体之间存在关联，这些突变体在表面基因的preS 2区域具有框内缺失。我们假设前S2突变的HBV基因组在HBV相关的致癌作用中起因果作用，因此这些突变体在患者中的出现可以作为HCC风险的早期标志。我们将通过证实前S2突变体和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用作慢性B型肝炎患者发生HCC风险增加的标志物。预计这些实验将提供前S2突变体作为慢性肝炎B中HCC风险标志物的可能效用的直接证据，以及在未来导致鉴定用于预防和/或治疗HCC的分子靶点。B型肝炎病毒通过引起肝损伤、肝硬化（肝瘢痕形成）以及最重要的肝癌，是世界上痛苦和死亡的主要原因。目前对肝癌的治疗是不够的，在很大程度上是因为我们无法及早发现癌症。我们希望我们的研究能够为这些患者的肝癌早期检测和治疗提供新的方法。

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.