Human papillomavirus integration perspective in small cell cervical carcinoma

Xiaoli Wang, Wenlong Jia, Mengyao Wang, Jihong Liu, Xianrong Zhou, Zhiqing Liang, Qinghua Zhang, Sixiang Long, Suolang Quzhen, Xiangchun Li, Qiang Tian, Xiong Li, Haiying Sun, Caili Zhao, Silu Meng, Ruoqi Ning, Ling Xi, Lin Wang, Shasha Zhou, Jianwei ZhangLi Wu, Yile Chen, Aijun Liu, Yaqi Ma, Xia Zhao, Xiaodong Cheng, Qing Zhang, Xiaobing Han, Huaxiong Pan, Yuan Zhang, Lili Cao, Yiqin Wang, Shaoping Ling, Lihua Cao, Hui Xing, Chang Xu, Long Sui, Shixuan Wang, Jianfeng Zhou, Beihua Kong, Xing Xie, Gang Chen*, Shuaicheng Li*, Ding Ma*, Shuang Li*

*Corresponding author for this work

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

15 Citations (Scopus)
45 Downloads (CityUHK Scholars)

Abstract

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3TACC3 and ANKRD12NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.
Original languageEnglish
Article number5968
JournalNature Communications
Volume13
Issue number1
Online published10 Oct 2022
DOIs
Publication statusPublished - 2022

Publisher's Copyright Statement

  • This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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