Abstract

Abstract It has been elucidated that hepatitis B virus (HBV) DNA is frequently integrated to some cancer related genes such as TERT or KMT2B in patients with chronic HBV infection. On the other hand, it has not yet become clear of the integration of HBV to the genome of patients with prior infection with HBV. To identify the integration sites of HBV, we performed next generation of target capture technology for hepatocellular carcinoma samples obtained from 73 HBc antibody positive patients but negative for HBs antigen nor hepatitis C antibody (HCV) (Group 1; prior infection), 78 HBs antigen positive patients (Group 2; positive control), and 33 patients without any antigens nor antibodies for HBV (Group 3; negative control). Among these patients, overall HBV integration in Group 2 (54 patients, 69.2%) was significantly frequent compared with that in Group 1 (12, 16.4%) (P < 0.001), and was not detected in any patients of Group 3. On the other hand, HBV integration occurred in the known driver genes; TERT in seven (9.5%) and 12 (15.3%) patients (P = 0.332), MLL4 in two (3.5%) and four (5.1%) patients (P = 682), and CCNE1 in 0 and one (1.2%) patient (P = 1.000) in Group 1 and 2, respectively. Notably, integration of any driver genes was not observed in 56 patients with prior infection with HBV who were positive for HCV infection.Taken together, despite the disappearance of HBV, the frequency of driver events by HBV integration in patients with prior HBV infection is similar to those with chronic HBV infection, and patients with prior HBV infection are still at the risk of hepatocellular carcinoma. Citation Format: Yutaka Midorikawa, Kenji Tatsuno, Shogo Yamamoto, Genta Nagae, Kazuhiko Koike, Mitsuhiko Moriyama, Tadatoshi Takayama, Kyoji Moriya, Hiroyuki Aburatani. Impact of virus integration into the genomes of hepatocellular carcinoma patients with prior hepatitis B virus infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 416.

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