Targeted long-read sequencing reveals clonally expanded HBV-associated chromosomal translocations in patients with chronic hepatitis B

• Published in: JHEP reports Vol. 4; no. 4; p. 100449
• Main Authors: van Buuren, Nicholas, Ramirez, Ricardo, Soulette, Cameron, Suri, Vithika, Han, Dong, May, Lindsey, Turner, Scott, Parvangada, P.C., Martin, Ross, Chan, Henry L.Y., Marcellin, Patrick, Buti, Maria, Bui, Nam, Bhardwaj, Neeru, Gaggar, Anuj, Li, Li, Mo, Hongmei, Feierbach, Becket
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022; Elsevier
• Subjects: Chromosomal translocations; Chronic HBV; Clonal expansion; Gastroenterology and Hepatology; Integrated HBV DNA; Long-read sequencing; Targeted sequencing; N/A; DNA-Seq; WGS; cccDNA; Long-read sequencing; Integrated HBV DNA; PEG-IFNα; Clonal expansion; rcDNA; TERT; FFPE; TDF; gDNA; DR1; HCC; Chronic HBV; contig; dslDNA; CCS; pgRNA; RNA-Seq; RIN; Chromosomal translocations; targeted Iso-Seq; NHEJ; Targeted sequencing; CHB; circular consensus sequence; formalin-fixed paraffin-embedded; direct repeat 1; hepatocellular carcinoma; chronic hepatitis B; RNA sequencing; genomic DNA; nucleos(t)ide analogue; pegylated interferon α; RNA integrity number; tenofovir disoproxil fumarate; pre-genomic RNA; whole genome sequencing; non-homologous end-joining; targeted long-read RNA-sequencing; contiguous sequence; telomerase reverse transcriptase; relaxed circular DNA; covalently closed circular DNA; DNA sequencing; double-stranded linear DNA; contig, contiguous sequence; N/A, nucleos(t)ide analogue; gDNA, genomic DNA; DR1, direct repeat 1; PEG-IFNα, pegylated interferon α; CHB, chronic hepatitis B; pgRNA, pre-genomic RNA; RIN, RNA integrity number; DNA-Seq, DNA sequencing; FFPE, formalin-fixed paraffin-embedded; NHEJ, non-homologous end-joining; TERT, telomerase reverse transcriptase; targeted Iso-Seq, targeted long-read RNA-sequencing; RNA-Seq, RNA sequencing; WGS, whole genome sequencing; dslDNA, double-stranded linear DNA; CCS, circular consensus sequence; TDF, tenofovir disoproxil fumarate; HCC, hepatocellular carcinoma; cccDNA, covalently closed circular DNA; rcDNA, relaxed circular DNA

HBV infects over 257 million people worldwide and is associated with the development of hepatocellular carcinoma (HCC). Integration of HBV DNA into the host genome is likely a key driver of HCC oncogenesis. Here, we utilise targeted long-read sequencing to determine the structure of HBV DNA integrat...