Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer

Liyuan Zhou, Qiongzi Qiu, Qing Zhou, Jianwei Li, Mengqian Yu, Kezhen Li, Lingling Xu, Xiaohui Ke, Haiming Xu, Bingjian Lu, Hui Wang, Weiguo Lu (), Pengyuan Liu () and Yan Lu ()
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Liyuan Zhou: Zhejiang University School of Medicine
Qiongzi Qiu: Zhejiang University School of Medicine
Qing Zhou: Zhejiang University School of Medicine
Jianwei Li: Zhejiang University School of Medicine
Mengqian Yu: Zhejiang University School of Medicine
Kezhen Li: Huazhong University of Science and Technology
Lingling Xu: Zhejiang University School of Medicine
Xiaohui Ke: Wenzhou Central Hospital
Haiming Xu: Zhejiang University
Bingjian Lu: Zhejiang University School of Medicine
Hui Wang: Zhejiang University School of Medicine
Weiguo Lu: Zhejiang University
Pengyuan Liu: Zhejiang University School of Medicine
Yan Lu: Zhejiang University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract Integration of human papillomavirus (HPV) DNA into the human genome is considered as a key event in cervical carcinogenesis. Here, we perform comprehensive characterization of large-range virus-human integration events in 16 HPV16-positive cervical tumors using the Nanopore long-read sequencing technology. Four distinct integration types characterized by the integrated HPV DNA segments are identified with Type B being particularly notable as lacking E6/E7 genes. We further demonstrate that multiple clonal integration events are involved in the use of shared breakpoints, the induction of inter-chromosomal translocations and the formation of extrachromosomal circular virus-human hybrid structures. Combined with the corresponding RNA-seq data, we highlight LINC00290, LINC02500 and LENG9 as potential driver genes in cervical cancer. Finally, we reveal the spatial relationship of HPV integration and its various structural variations as well as their functional consequences in cervical cancer. These findings provide insight into HPV integration and its oncogenic progression in cervical cancer.

Date: 2022
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DOI: 10.1038/s41467-022-30190-1

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