Details

Autor(en) / Beteiligte

• Hu, Zheng
• Zhu, Da
• Wang, Wei
• Li, Weiyang
• Jia, Wenlong
• Zeng, Xi
• Ding, Wencheng
• Yu, Lan
• Wang, Xiaoli
• Wang, Liming
• Shen, Hui
• Zhang, Changlin
• Liu, Hongjie
• Liu, Xiao
• Zhao, Yi
• Fang, Xiaodong
• Li, Shuaicheng
• Chen, Wei
• Tang, Tang
• Fu, Aisi
• Wang, Zou
• Chen, Gang
• Gao, Qinglei
• Li, Shuang
• Xi, Ling
• Wang, Changyu
• Liao, Shujie
• Ma, Xiangyi
• Wu, Peng
• Li, Kezhen
• Wang, Shixuan
• Zhou, Jianfeng
• Wang, Jun
• Xu, Xun
• Wang, Hui
• Ma, Ding

Titel

Genome-wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology-mediated integration mechanism

Ist Teil von

• Nature genetics, 2015-02, Vol.47 (2), p.158-163

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Ding Ma, Hui Wang, Xun Xu and colleagues report a genome-wide map of HPV integration sites in cervical cancer samples and cell lines. In addition to discovering new integration hot spots, the authors identify microhomology-mediated DNA repair as a likely mechanism by which HPV integrates into the human genome. 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.