Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma.
Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma.
复制标题
肝细胞癌中 HBV 整合的基因组和致癌偏好
DOI：
10.1038/ncomms12992
复制
发表时间：
2016-10-05
影响因子：
16.6
通讯作者：
Wang HY
中科院分区：
文献类型：
--
作者：
Zhao LH;Liu X;Yan HX;Li WY;Zeng X;Yang Y;Zhao J;Liu SP;Zhuang XH;Lin C;Qin CJ;Zhao Y;Pan ZY;Huang G;Liu H;Zhang J;Wang RY;Yang Y;Wen W;Lv GS;Zhang HL;Wu H;Huang S;Wang MD;Tang L;Cao HZ;Wang L;Lee TL;Jiang H;Tan YX;Yuan SX;Hou GJ;Tao QF;Xu QG;Zhang XQ;Wu MC;Xu X;Wang J;Yang HM;Zhou WP;Wang HY
B型肝炎病毒（HBV）可整合到人类基因组中，导致基因组不稳定和肝癌发生。通过进行高通量病毒整合检测和RNA测序，我们在426例HCC患者的肿瘤和邻近非肿瘤样本中确定了4，225个HBV整合事件。我们发现，HBV易于整合到罕见的脆性位点和功能基因组区域，包括CpG岛。我们观察到一个独特的模式，在肿瘤和非肿瘤组织之间的HBV整合的优惠网站。HBV插入位点在肿瘤中端粒附近显著富集。复发性HBV靶基因被鉴定为很少有重叠。总体HBV整合频率在男性肿瘤基因组中比女性高得多，整合到17号染色体中的显著富集。此外，还观察到了一种依赖于HBV整合模式，影响不同的靶基因。我们的数据表明，HBV整合有很高的潜力，以推动致癌转化。
Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.
登录
查看更多内容
影响因子：
4.5
作者：
Verdin H;D'haene B;Beysen D;Novikova Y;Menten B;Sante T;Lapunzina P;Nevado J;Carvalho CM;Lupski JR;De Baere E
通讯作者：
De Baere E
影响因子：
11.2
作者：
Cunningham, Steven C.;Gallmeier, Eike;Kern, Scott E.
通讯作者：
Kern, Scott E.
影响因子：
14.9
作者：
Bailey SM;Murnane JP
通讯作者：
Murnane JP
影响因子：
50.3
作者：
Lau, Chi-Chiu;Sun, Tingting;Wong, Nathalie
通讯作者：
Wong, Nathalie
影响因子：
25.7
作者：
Li, Xiaojun;Zhang, Jiangbo;Lu, Fengmin
通讯作者：
Lu, Fengmin