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 Zhang, Li 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 () and Shuang Li ()
Additional contact information
Xiaoli Wang: Huazhong University of Science and Technology
Wenlong Jia: City University of Hong Kong Shenzhen Research Institute
Mengyao Wang: City University of Hong Kong Shenzhen Research Institute
Jihong Liu: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Xianrong Zhou: Obstetrics and Gynecology Hospital of Fudan University
Zhiqing Liang: Third Military Medical University
Qinghua Zhang: The Central Hospital of Wuhan
Sixiang Long: Huazhong University of Science and Technology
Suolang Quzhen: Huazhong University of Science and Technology
Xiangchun Li: Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital
Qiang Tian: National Infrastructures of Translational Medicine (Shanghai), Shanghai JiaoTong University School of Medicine
Xiong Li: Huazhong University of Science and Technology
Haiying Sun: Huazhong University of Science and Technology
Caili Zhao: Huazhong University of Science and Technology
Silu Meng: Huazhong University of Science and Technology
Ruoqi Ning: Huazhong University of Science and Technology
Ling Xi: Huazhong University of Science and Technology
Lin Wang: Huazhong University of Science and Technology
Shasha Zhou: Huazhong University of Science and Technology
Jianwei Zhang: Huazhong University of Science and Technology
Li Wu: Hunan ProvinceTumor Hospital
Yile Chen: Hunan ProvinceTumor Hospital
Aijun Liu: Chinese People’s Liberation Army General Hospital
Yaqi Ma: Chinese People’s Liberation Army General Hospital
Xia Zhao: Sichuan University
Xiaodong Cheng: Women’s Reproductive Health Laboratory of Zhejiang Province
Qing Zhang: Shandong University
Xiaobing Han: the First Affiliated Hospital, Medical School of Xi’an Jiaotong University
Huaxiong Pan: Huazhong University of Science and Technology
Yuan Zhang: Huazhong University of Science and Technology
Lili Cao: The Central Hospital of Wuhan
Yiqin Wang: Third Military Medical University
Shaoping Ling: Genome Wisdom Inc.
Lihua Cao: Genome Wisdom Inc.
Hui Xing: Huazhong University of Science and Technology
Chang Xu: City University of Hong Kong Shenzhen Research Institute
Long Sui: Obstetrics and Gynecology Hospital of Fudan University
Shixuan Wang: Huazhong University of Science and Technology
Jianfeng Zhou: Huazhong University of Science and Technology
Beihua Kong: Shandong University
Xing Xie: Women’s Reproductive Health Laboratory of Zhejiang Province
Gang Chen: Huazhong University of Science and Technology
Shuaicheng Li: City University of Hong Kong Shenzhen Research Institute
Ding Ma: Huazhong University of Science and Technology
Shuang Li: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: 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 (FGFR3–TACC3 and ANKRD12–NDUFV2), 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.

Date: 2022
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DOI: 10.1038/s41467-022-33359-w

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