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10780432ccr210002-sup-258182_3_supp_7039727_qr8732.xlsx (570.98 kB)

Table S6 from The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients

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posted on 2023-03-31, 22:43 authored by Bo Zheng, Xiao-Long Liu, Rong Fan, Jian Bai, Hao Wen, Lu-Tao Du, Guo-Qing Jiang, Chun-Ying Wang, Xiao-Tang Fan, Yi-Nong Ye, Yun-Song Qian, Ying-Chao Wang, Gao-Jing Liu, Guo-Hong Deng, Feng Shen, He-Ping Hu, Hui Wang, Qing-Zheng Zhang, Lan-Lan Ru, Jing Zhang, Yan-Hang Gao, Jie Xia, Hua-Dong Yan, Min-Feng Liang, Yan-Long Yu, Fu-Ming Sun, Yu-Jing Gao, Jian Sun, Chun-Xiu Zhong, Yin Wang, Fei Kong, Jin-Ming Chen, Dan Zheng, Yuan Yang, Chuan-Xin Wang, Lin Wu, Jin-Lin Hou, Jing-Feng Liu, Hong-Yang Wang, Lei Chen

Table S6

Funding

National Research Program of China

State Key Project for Liver Cancer

National Natural Science Foundation of China

National Natural Science Foundation of Shanghai

History

ARTICLE ABSTRACT

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. 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. 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. 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.

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