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Human papillomavirus integration perspective in small cell cervical carcinoma

Author

Listed:
  • Xiaoli Wang

    (Huazhong University of Science and Technology
    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
    Huazhong University of Science and Technology)

  • Suolang Quzhen

    (Huazhong University of Science and Technology
    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
    Huazhong University of Science and Technology
    The Central Hospital of Wuhan)

  • Haiying Sun

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Caili Zhao

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Silu Meng

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Ruoqi Ning

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Ling Xi

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Lin Wang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Shasha Zhou

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Jianwei Zhang

    (Huazhong University of Science and Technology
    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
    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
    Huazhong University of Science and Technology)

  • Shuaicheng Li

    (City University of Hong Kong Shenzhen Research Institute)

  • Ding Ma

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Shuang Li

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

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.

Suggested Citation

  • 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 , 2022. "Human papillomavirus integration perspective in small cell cervical carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33359-w
    DOI: 10.1038/s41467-022-33359-w
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    References listed on IDEAS

    as
    1. Akinyemi I. Ojesina & Lee Lichtenstein & Samuel S. Freeman & Chandra Sekhar Pedamallu & Ivan Imaz-Rosshandler & Trevor J. Pugh & Andrew D. Cherniack & Lauren Ambrogio & Kristian Cibulskis & Bjørn Bert, 2014. "Landscape of genomic alterations in cervical carcinomas," Nature, Nature, vol. 506(7488), pages 371-375, February.
    2. Andrew Adey & Joshua N. Burton & Jacob O. Kitzman & Joseph B. Hiatt & Alexandra P. Lewis & Beth K. Martin & Ruolan Qiu & Choli Lee & Jay Shendure, 2013. "The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line," Nature, Nature, vol. 500(7461), pages 207-211, August.
    Full references (including those not matched with items on IDEAS)

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