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Characterization of hepatitis B virus infection and viral DNA integration in non-Hodgkin lymphoma |
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| Authors: | Mengge Li Yuling Shen Yiming Chen Haifeng Gao Jiaqin Zhou Qing Wang Chunsun Fan Wei Zhang Jin Li Hui Cong Jinyang Gu Yu Gan Hong Tu |
| Affiliation: | 1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;2. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Head and Neck Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;3. Department of Pathology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;4. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China;5. Department of Head and Neck Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;6. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of etiology, Qidong People's Hospital/Qidong Liver Cancer Institute, Qidong, China;7. Department of Transplantation, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China |
| Abstract: | Hepatitis B virus (HBV) infection has been reported to be associated with non-Hodgkin lymphoma (NHL). However, the evidence is limited to the seroepidemiological study. There is a lack of evidence showing the HBV infection and integration in NHL cells. Here, we reported that in the Shanghai area, the positive rates of serum HBsAg (OR: 3.11; 95% CI: 2.20-4.41) and HBeAg (OR: 3.99; 95% CI: 1.73-9.91) were significantly higher in patients with NHL. HBsAg, HBcAg and HBV DNA were detected in 34.4%, 45.2% and 47.0% of the NHL tissues, respectively. Furthermore, by using a high-throughput viral integration detection approach (HIVID), integrated HBV DNA was identified from 50% (6/12) HBV-related NHL tissues. There were a total of 313 HBV integration sites isolated from the NHL tissues, among which four protein-coding genes (FAT2, SETX, ITGA10 and CD63) were interrupted by HBV DNA in their exons. Seven HBV preferential target genes (ANKS1B, HDAC4, EGFLAM, MAN1C1, XKR6, ZBTB38 and CCDC91) showed significantly altered expression levels in NHL, suggesting a potential role of these genes in NHL development. Taken together, HBV integration is a common phenomenon in NHL. This finding opens up a new direction of research into the mechanistic link between HBV infection and NHL. |
| Keywords: | hepatitis B virus integration non-Hodgkin lymphoma |