Singapore: Scientists at the Genome Institute of Singapore (GIS) have unraveled the mechanism that causes liver cancer (hepatocellular carcinoma, HCC), one of the most common solid tumors worldwide. This genome-wide research was done in collaboration with colleagues from the National University of Singapore (NUS), University of Hong Kong, Eli Lilly, Merck Research Laboratories USA, Pfizer Oncology USA and Beijing Genomics Institute China.

One major cause of liver cancer, or HCC, is high exposure to the hepatitis B virus (HBV), resulting in the integration of HBV into the victim's genes. Individuals who carry the HBV have a greater than 100-fold increased relative risk of developing HCC, considered to be a serious global health problem by the World Health Organization.

Due to technology and sample limitations in the past, only restricted results were found. In this study, the scientists leveraged on massively parallel sequencing technology to survey the HBV integrations on paired tumor and adjacent non-tumor tissues from 88 Chinese HCC patients.

Their analyses revealed that the incidences of HBV integrations were high — 76 of the 88 patients had HBV integration. Specifically, they discovered that the HBV will integrate into genes CCNE1, SENP5 and ROCK1, causing an increase in the expression levels in these genes, and subsequently enhancing the tumor growth. This discovery is in addition to the previously reported integration into the TERT and MLL4 genes.

The scientists also observed that HBV integration induced chromosome instability, resulting in the scrambling of the genome.