The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients
Menée sur les génomes tumoraux et non tumoraux de 4 patients atteints d'un carcinome hépatocellulaire, cette étude de séquençage dresse la cartographie des anomalies de l'ADN des cellules tumorales induites par l'intégration du génome du virus de l'hépatite B
Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor and non-tumor genomes (>80X coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240X coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals.
Genome Research , article en libre accès, 2012