期刊
NATURE GENETICS
卷 47, 期 2, 页码 158-163出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3178
关键词
-
资金
- National Development Program (973) for the Key Basic Research of China [2015CB553903, 2013CB911304]
- National Natural Science Funding of China [81230038, 81372805, 81172466, 81272859, 81372801, 81372804, 81402158, 81372806, 81370469, 81172468, 81101964, 81230052, 81302266]
- Chinese 863 Program [2012AA02A507, 2012AA02A201]
- Guangdong Enterprise Key Laboratory of Human Disease Genomics
- ShenZhen Engineering Laboratory for Clinical Molecular Diagnostic
- China National GeneBank-Shenzhen
Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis(1). 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(2). Our data provide insights into HPV integration-driven cervical carcinogenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据