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Characterization of somatic structural variations in 528 Chinese individuals with Esophageal squamous cell carcinoma

Author

Listed:
  • Heyang Cui

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory
    Shanxi Medical University)

  • Yong Zhou

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory
    City University of Hong Kong Shenzhen Research Institute)

  • Fang Wang

    (Shanxi Medical University)

  • Caixia Cheng

    (The First Hospital, Shanxi Medical University)

  • Weimin Zhang

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory
    Peking University Cancer Hospital & Institute
    Chinese Academy of Medical Sciences)

  • Ruifang Sun

    (Shanxi Provincial Cancer Hospital)

  • Ling Zhang

    (Shanxi Medical University)

  • Yanghui Bi

    (Shanxi Medical University)

  • Min Guo

    (Shanxi Medical University)

  • Yan Zhou

    (Shanxi Medical University)

  • Xinhui Wang

    (Shanxi Medical University)

  • Jiaxin Ren

    (The First Hospital, Shanxi Medical University)

  • Ruibing Bai

    (The First Hospital, Shanxi Medical University)

  • Ning Ding

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Chen Cheng

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Longlong Wang

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Xuehan Zhuang

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Mingwei Gao

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Yongjia Weng

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Yueguang Wu

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory)

  • Huijuan Liu

    (Shanxi Medical University)

  • Shuaicheng Li

    (City University of Hong Kong Shenzhen Research Institute)

  • Shubin Wang

    (Peking University Shenzhen Hospital, Shenzhen-Peking University-Hong Kong University of Science and Technology Medical Center)

  • Xiaolong Cheng

    (Shanxi Medical University)

  • Yongping Cui

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory
    Shanxi Medical University)

  • Zhihua Liu

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Qimin Zhan

    (Peking University Shenzhen Hospital, Shenzhen Peking University-the Hong Kong University of Science and Technology (PKU-HKUST) Medical Center; Institute of Cancer Research, Shenzhen Bay Laboratory
    Peking University Cancer Hospital & Institute
    Chinese Academy of Medical Sciences)

Abstract

Esophageal squamous cell carcinoma (ESCC) demonstrates high genome instability. Here, we analyze 528 whole genomes to investigate structural variations’ mechanisms and biological functions. SVs show multi-mode distributions in size, indicating distinct mutational processes. We develop a tool and define five types of complex rearrangements with templated insertions. We highlight a type of fold-back inversion, which is associated with poor outcomes. Distinct rearrangement signatures demonstrate variable genomic metrics such as replicating time, spatial proximity, and chromatin accessibility. Specifically, fold-back inversion tends to occur near the centrosome; TD-c2 (Tandem duplication-cluster2) is significantly enriched in chromatin-accessibility and early-replication region compared to other signatures. Analyses of TD-c2 signature reveal 9 TD hotspots, of which we identify a hotspot consisting of a super-enhancer of PTHLH. We confirm the oncogenic effect of the PTHLH gene and its interaction with enhancers through functional experiments. Finally, extrachromosomal circular DNAs (ecDNAs) are present in 14% of ESCCs and have strong selective advantages to driver genes.

Suggested Citation

  • Heyang Cui & Yong Zhou & Fang Wang & Caixia Cheng & Weimin Zhang & Ruifang Sun & Ling Zhang & Yanghui Bi & Min Guo & Yan Zhou & Xinhui Wang & Jiaxin Ren & Ruibing Bai & Ning Ding & Chen Cheng & Longlo, 2022. "Characterization of somatic structural variations in 528 Chinese individuals with Esophageal squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33994-3
    DOI: 10.1038/s41467-022-33994-3
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    References listed on IDEAS

    as
    1. Monkol Lek & Konrad J. Karczewski & Eric V. Minikel & Kaitlin E. Samocha & Eric Banks & Timothy Fennell & Anne H. O’Donnell-Luria & James S. Ware & Andrew J. Hill & Beryl B. Cummings & Taru Tukiainen , 2016. "Analysis of protein-coding genetic variation in 60,706 humans," Nature, Nature, vol. 536(7616), pages 285-291, August.
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    1. Shixiang Wang & Chen-Yi Wu & Ming-Ming He & Jia-Xin Yong & Yan-Xing Chen & Li-Mei Qian & Jin-Ling Zhang & Zhao-Lei Zeng & Rui-Hua Xu & Feng Wang & Qi Zhao, 2024. "Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Amr M. Al-Zain & Mattie R. Nester & Iffat Ahmed & Lorraine S. Symington, 2023. "Double-strand breaks induce inverted duplication chromosome rearrangements by a DNA polymerase δ-dependent mechanism," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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