IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30190-1.html
   My bibliography  Save this article

Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer

Author

Listed:
  • Liyuan Zhou

    (Zhejiang University School of Medicine)

  • Qiongzi Qiu

    (Zhejiang University School of Medicine)

  • Qing Zhou

    (Zhejiang University School of Medicine)

  • Jianwei Li

    (Zhejiang University School of Medicine)

  • Mengqian Yu

    (Zhejiang University School of Medicine)

  • Kezhen Li

    (Huazhong University of Science and Technology)

  • Lingling Xu

    (Zhejiang University School of Medicine)

  • Xiaohui Ke

    (Wenzhou Central Hospital)

  • Haiming Xu

    (Zhejiang University)

  • Bingjian Lu

    (Zhejiang University School of Medicine
    Zhejiang University)

  • Hui Wang

    (Zhejiang University School of Medicine
    Zhejiang University)

  • Weiguo Lu

    (Zhejiang University
    Zhejiang University School of Medicine)

  • Pengyuan Liu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University School of Medicine
    Medical College of Wisconsin)

  • Yan Lu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University School of Medicine)

Abstract

Integration of human papillomavirus (HPV) DNA into the human genome is considered as a key event in cervical carcinogenesis. Here, we perform comprehensive characterization of large-range virus-human integration events in 16 HPV16-positive cervical tumors using the Nanopore long-read sequencing technology. Four distinct integration types characterized by the integrated HPV DNA segments are identified with Type B being particularly notable as lacking E6/E7 genes. We further demonstrate that multiple clonal integration events are involved in the use of shared breakpoints, the induction of inter-chromosomal translocations and the formation of extrachromosomal circular virus-human hybrid structures. Combined with the corresponding RNA-seq data, we highlight LINC00290, LINC02500 and LENG9 as potential driver genes in cervical cancer. Finally, we reveal the spatial relationship of HPV integration and its various structural variations as well as their functional consequences in cervical cancer. These findings provide insight into HPV integration and its oncogenic progression in cervical cancer.

Suggested Citation

  • Liyuan Zhou & Qiongzi Qiu & Qing Zhou & Jianwei Li & Mengqian Yu & Kezhen Li & Lingling Xu & Xiaohui Ke & Haiming Xu & Bingjian Lu & Hui Wang & Weiguo Lu & Pengyuan Liu & Yan Lu, 2022. "Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30190-1
    DOI: 10.1038/s41467-022-30190-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30190-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30190-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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. Jesse R. Dixon & Siddarth Selvaraj & Feng Yue & Audrey Kim & Yan Li & Yin Shen & Ming Hu & Jun S. Liu & Bing Ren, 2012. "Topological domains in mammalian genomes identified by analysis of chromatin interactions," Nature, Nature, vol. 485(7398), pages 376-380, May.
    3. Yilong Li & Nicola D. Roberts & Jeremiah A. Wala & Ofer Shapira & Steven E. Schumacher & Kiran Kumar & Ekta Khurana & Sebastian Waszak & Jan O. Korbel & James E. Haber & Marcin Imielinski & Joachim We, 2020. "Patterns of somatic structural variation in human cancer genomes," Nature, Nature, vol. 578(7793), pages 112-121, February.
    4. Daniel C. Jeffares & Clemency Jolly & Mimoza Hoti & Doug Speed & Liam Shaw & Charalampos Rallis & Francois Balloux & Christophe Dessimoz & Jürg Bähler & Fritz J. Sedlazeck, 2017. "Transient structural variations have strong effects on quantitative traits and reproductive isolation in fission yeast," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    5. Ka-Wei Tang & Babak Alaei-Mahabadi & Tore Samuelsson & Magnus Lindh & Erik Larsson, 2013. "The landscape of viral expression and host gene fusion and adaptation in human cancer," Nature Communications, Nature, vol. 4(1), pages 1-9, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jinhyun Kim & Sungsik Kim & Huiran Yeom & Seo Woo Song & Kyoungseob Shin & Sangwook Bae & Han Suk Ryu & Ji Young Kim & Ahyoun Choi & Sumin Lee & Taehoon Ryu & Yeongjae Choi & Hamin Kim & Okju Kim & Yu, 2023. "Barcoded multiple displacement amplification for high coverage sequencing in spatial genomics," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Alexander Martinez-Fundichely & Austin Dixon & Ekta Khurana, 2022. "Modeling tissue-specific breakpoint proximity of structural variations from whole-genomes to identify cancer drivers," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Zhuoran Xu & Quan Li & Luigi Marchionni & Kai Wang, 2023. "PhenoSV: interpretable phenotype-aware model for the prioritization of genes affected by structural variants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Zhen-Hui Wang & Xin-Feng Wang & Tianyuan Lu & Ming-Rui Li & Peng Jiang & Jing Zhao & Si-Tong Liu & Xue-Qi Fu & Jonathan F. Wendel & Yves Peer & Bao Liu & Lin-Feng Li, 2022. "Reshuffling of the ancestral core-eudicot genome shaped chromatin topology and epigenetic modification in Panax," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Michelle Dietzen & Haoran Zhai & Olivia Lucas & Oriol Pich & Christopher Barrington & Wei-Ting Lu & Sophia Ward & Yanping Guo & Robert E. Hynds & Simone Zaccaria & Charles Swanton & Nicholas McGranaha, 2024. "Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Bhuwan Khatri & Kandice L. Tessneer & Astrid Rasmussen & Farhang Aghakhanian & Tove Ragna Reksten & Adam Adler & Ilias Alevizos & Juan-Manuel Anaya & Lara A. Aqrawi & Eva Baecklund & Johan G. Brun & S, 2022. "Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Alon Diament & Tamir Tuller, 2015. "Improving 3D Genome Reconstructions Using Orthologous and Functional Constraints," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-22, May.
    10. Andrea Wilderman & Eva D’haene & Machteld Baetens & Tara N. Yankee & Emma Wentworth Winchester & Nicole Glidden & Ellen Roets & Jo Dorpe & Sandra Janssens & Danny E. Miller & Miranda Galey & Kari M. B, 2024. "A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    11. Yu Chen & Amy Y. Wang & Courtney A. Barkley & Yixin Zhang & Xinyang Zhao & Min Gao & Mick D. Edmonds & Zechen Chong, 2023. "Deciphering the exact breakpoints of structural variations using long sequencing reads with DeBreak," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Brent S. Perlman & Noah Burget & Yeqiao Zhou & Gregory W. Schwartz & Jelena Petrovic & Zora Modrusan & Robert B. Faryabi, 2024. "Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    13. Brault, Vincent & Ouadah, Sarah & Sansonnet, Laure & Lévy-Leduc, Céline, 2018. "Nonparametric multiple change-point estimation for analyzing large Hi-C data matrices," Journal of Multivariate Analysis, Elsevier, vol. 165(C), pages 143-165.
    14. Seungsoo Hahn & Dongsup Kim, 2015. "Identifying and Reducing Systematic Errors in Chromosome Conformation Capture Data," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-17, December.
    15. Julia Minderjahn & Alexander Fischer & Konstantin Maier & Karina Mendes & Margit Nuetzel & Johanna Raithel & Hanna Stanewsky & Ute Ackermann & Robert Månsson & Claudia Gebhard & Michael Rehli, 2022. "Postmitotic differentiation of human monocytes requires cohesin-structured chromatin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Pau Farré & Eldon Emberly, 2018. "A maximum-entropy model for predicting chromatin contacts," PLOS Computational Biology, Public Library of Science, vol. 14(2), pages 1-16, February.
    17. Anastasiya Kishkevich & Sanjeeta Tamang & Michael O. Nguyen & Judith Oehler & Elena Bulmaga & Christos Andreadis & Carl A. Morrow & Manisha Jalan & Fekret Osman & Matthew C. Whitby, 2022. "Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Wu Zuo & Guangming Chen & Zhimei Gao & Shuai Li & Yanyan Chen & Chenhui Huang & Juan Chen & Zhengjun Chen & Ming Lei & Qian Bian, 2021. "Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    19. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Yingyan Yu & Zhen Zhang & Xiaorui Dong & Ruixin Yang & Zhongqu Duan & Zhen Xiang & Jun Li & Guichao Li & Fazhe Yan & Hongzhang Xue & Du Jiao & Jinyuan Lu & Huimin Lu & Wenmin Zhang & Yangzhen Wei & Sh, 2022. "Pangenomic analysis of Chinese gastric cancer," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30190-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.