Publication Date:
2015-01-29
Description:
Nature Genetics 47, 158 (2015). doi:10.1038/ng.3178 Authors: Zheng Hu, Da Zhu, Wei Wang, Weiyang Li, Wenlong Jia, Xi Zeng, Wencheng Ding, Lan Yu, Xiaoli Wang, Liming Wang, Hui Shen, Changlin Zhang, Hongjie Liu, Xiao Liu, Yi Zhao, Xiaodong Fang, Shuaicheng Li, Wei Chen, Tang Tang, Aisi Fu, Zou Wang, Gang Chen, Qinglei Gao, Shuang Li, Ling Xi, Changyu Wang, Shujie Liao, Xiangyi Ma, Peng Wu, Kezhen Li, Shixuan Wang, Jianfeng Zhou, Jun Wang, Xun Xu, Hui Wang & Ding Ma Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways. Our data provide insights into HPV integration-driven cervical carcinogenesis.
Print ISSN:
1061-4036
Electronic ISSN:
1546-1718
Topics:
Biology
,
Medicine
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