BGI, Asian Cancer Research Group publish genome-wide study of hep B virus

SHENZEN, China—BGI and the Asian Cancer Research Group havepublished the results of a whole genome-wide study of recurrent hepatitis Bvirus (HBV) integration in hepatocellular carcinoma (HCC). According to theauthors of the study, which was published in Nature Genetics, their results provide important insights that maybe used to improve diagnosis and treatment of HCC, the most common form ofliver cancer worldwide.

"This study provided new insight into mechanisms of HBVintegration, which promote liver cancer and affect clinical outcomes," said Dr.Ken Sung, lead author of the publication, National University of Singapore andhonorary associate professor of Hong Kong University. "We expect furtherinvestigation may lead to improved diagnosis and treatment of HCC."

The collaborators carried out whole-genome sequencing in alarge sample cohort of Chinese patients with HCC to characterize genomeintegration patterns and determine the prevalence of integrated HBV. Throughthe sequencing and analysis, researchers found that HBV integration was acommon event in liver tumors and was observed more frequently in tumors (86.4percent) than in adjacent normal liver tissues (30.7 percent). In addition tothe previously reported TERT and MLL4 genes, researchers discovered three novelgenes (CCNE1, SENP5 and ROCK1) associated with recurrent HBV integrations, eachof which are known to play an important role in cancer development andprogression.

Researchers also observed that the number of HBV integrationevents (recurrences) is positively associated with the tumor size, serum HBsAgand α-fetoprotein level. Patients with no or low numbers of detected HBVintegrations in their tumor survived longer than those with a high number ofHBV integrations, suggesting that HBV integration events are a negativeprognostic indicator in HCC patients.

The researchers indicated that HBV integrations have somecharacteristics that may help the virus to control specific genes in the hosttumor. They found HBV integration sites are typically found close to or insideof the targeted genes, which may be a mechanism for HBV to control theexpression of some oncogenes or tumor suppressor genes. More than 40 percent ofthe integrations were observed to break the HBV genome at position 1,800 andintegrate into the human genome. This may be due to the fact that the HBVenhancer and the HBV ORF replication sites are found at this locus. Moreover,they observed that HBV integrations correlated with increased DNA copy numberaround HBV integration breakpoints, which provides evidence that HBVintegration initializes the chromosomal instability of the HCC genome.

"This study is of great interest to the scientificcommunity, which is working toward better understanding HBV integration inHCC," said Hancheng Zheng, primary investigator of this project at BGI. "Basedon these results, we can better explore the detailed molecular mechanism andclinical impact of HBV integration, promoting the discovery and development offuture liver cancer treatments."

The Asian Cancer Research Group is an independent, not-for-profitcompany established by Eli Lilly & Co., Merck and Pfizer Inc.