HBV VIS Detail Information

> This page shows VIS [1032792] detail information, including site information (chromosome, GRCh38 location, disease, sample, etc) and literature information.

Site Information

DVID	1032792
Chromosome	chr1
GRCh38 Location	36464126
Disease	Carcinoma, Hepatocellular

Literature Information

PubMed PMID	33947693
Year	2021 Jul 1;27(13):3772-3783
Journal	Clinical cancer research : an official journal of the American Association for Cancer Research
Title	The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.
Author	Zheng B,Liu XL,Fan R,Bai J,Wen H,Du LT,Jiang GQ,Wang CY,Fan XT,Ye YN,Qian YS,Wang YC,Liu GJ,Deng GH,Shen F,Hu HP,Wang H,Zhang QZ,Ru LL,Zhang J,Gao YH,Xia J,Yan HD,Liang MF,Yu YL,Sun FM,Gao YJ,Sun J,Zhong CX,Wang Y,Kong F,Chen JM,Zheng D,Yang Y,Wang CX,Wu L,Hou JL,Liu JF,Wang HY,Chen L
Evidence	PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.