Genome-wide profiling of Epstein-Barr virus integration by targeted sequencing in Epstein-Barr virus associated malignancies

作者：Miao Xu, Weilong Zhang, Qing Zhu, Youyuan Yao, Qi‐Sheng Feng, Zhe Zhang, Roujun Peng, Wei‐Hua Jia, Gui-Ping He, Lin Feng, Zhao-Lei Zeng, Bing Luo, Rui‐Hua Xu, Mu‐Sheng Zeng, Weili Zhao, Sai‐Juan Chen, Yi‐Xin Zeng, Yuchen Jiao · 发表于：Theranostics · 年份：2019 · DOI：10.7150/thno.29622 · 被引用次数：83 · 研究领域：Viral-associated cancers and disorders、Lymphoma Diagnosis and Treatment、Cholangiocarcinoma and Gallbladder Cancer Studies

Rationale: Epstein-Barr virus (EBV) is associated with multiple malignancies with expression of viral oncogenic proteins and chronic inflammation as major mechanisms contributing to tumor development. A less well-studied mechanism is the integration of EBV into the human genome possibly at sites which may disrupt gene expression or genome stability. Methods: We sequenced tumor DNA to profile the EBV sequences by hybridization-based enrichment. Bioinformatic analysis was used to detect the breakpoints of EBV integrations in the genome of cancer cells. Results: We identified 197 breakpoints in nasopharyngeal carcinomas and other EBV-associated malignancies. EBV integrations were enriched at vulnerable regions of the human genome and were close to tumor suppressor and inflammation-related genes. We found that EBV integrations into the introns could decrease the expression of the inflammation-related genes, TNFAIP3, PARK2, and CDK15, in NPC tumors. In the EBV genome, the breakpoints were frequently at oriP or terminal repeats. These breakpoints were surrounded by microhomology sequences, consistent with a mechanism for integration involving viral genome replication and microhomology-mediated recombination.