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The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers

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  • Yaodong Zhang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Zijian Ma

    (Nanjing Medical University)

  • Changxian Li

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Cheng Wang

    (Nanjing Medical University
    Nanjing Medical University
    Nanjing Medical University)

  • Wangjie Jiang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Jiang Chang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Sheng Han

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Zefa Lu

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Zicheng Shao

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Yirui Wang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Hongwei Wang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Chenyu Jiao

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Dong Wang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Xiaofeng Wu

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Hongbing Shen

    (Nanjing Medical University
    Nanjing Medical University)

  • Xuehao Wang

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

  • Zhibin Hu

    (Nanjing Medical University
    Nanjing Medical University
    Nanjing Medical University)

  • Xiangcheng Li

    (The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Liver Transplantation)

Abstract

Molecular variation between geographical populations and subtypes indicate potential genomic heterogeneity and novel genomic features within CCA. Here, we analyze exome-sequencing data of 87 perihilar cholangiocarcinoma (pCCA) and 261 intrahepatic cholangiocarcinoma (iCCA) cases from 3 Asian centers (including 43 pCCAs and 24 iCCAs from our center). iCCA tumours demonstrate a higher tumor mutation burden and copy number alteration burden (CNAB) than pCCA tumours, and high CNAB indicates a poorer pCCA prognosis. We identify 12 significantly mutated genes and 5 focal CNA regions, and demonstrate common mutations in post-transcriptional modification-related potential driver genes METTL14 and RBM10 in pCCA tumours. Finally we demonstrate the tumour-suppressive role of METTL14, a major RNA N6-adenosine methyltransferase (m6A), and illustrate that its loss-of-function mutation R298H may act through m6A modification on potential driver gene MACF1. Our results may be valuable for better understanding of how post-transcriptional modification can affect CCA development, and highlight both similarities and differences between pCCA and iCCA.

Suggested Citation

  • Yaodong Zhang & Zijian Ma & Changxian Li & Cheng Wang & Wangjie Jiang & Jiang Chang & Sheng Han & Zefa Lu & Zicheng Shao & Yirui Wang & Hongwei Wang & Chenyu Jiao & Dong Wang & Xiaofeng Wu & Hongbing , 2022. "The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30708-7
    DOI: 10.1038/s41467-022-30708-7
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    as
    1. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Correction: Corrigendum: Signatures of mutational processes in human cancer," Nature, Nature, vol. 502(7470), pages 258-258, October.
    2. Michael S. Lawrence & Petar Stojanov & Paz Polak & Gregory V. Kryukov & Kristian Cibulskis & Andrey Sivachenko & Scott L. Carter & Chip Stewart & Craig H. Mermel & Steven A. Roberts & Adam Kiezun & Pe, 2013. "Mutational heterogeneity in cancer and the search for new cancer-associated genes," Nature, Nature, vol. 499(7457), pages 214-218, July.
    3. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Signatures of mutational processes in human cancer," Nature, Nature, vol. 500(7463), pages 415-421, August.
    4. Wei Wang & Fei Shao & Xueying Yang & Juhong Wang & Rongxuan Zhu & Yannan Yang & Gaoxiang Zhao & Dong Guo & Yingli Sun & Jie Wang & Qi Xue & Shugeng Gao & Yibo Gao & Jie He & Zhimin Lu, 2021. "METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N6-methyladenosine-dependent YTHDF binding," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    5. Wei Wang & Fei Shao & Xueying Yang & Juhong Wang & Rongxuan Zhu & Yannan Yang & Gaoxiang Zhao & Dong Guo & Yingli Sun & Jie Wang & Qi Xue & Shugeng Gao & Yibo Gao & Jie He & Zhimin Lu, 2021. "Author Correction: METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N6-methyladenosine-dependent YTHDF binding," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
    6. Xiang Wang & Jing Feng & Yuan Xue & Zeyuan Guan & Delin Zhang & Zhu Liu & Zhou Gong & Qiang Wang & Jinbo Huang & Chun Tang & Tingting Zou & Ping Yin, 2016. "Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex," Nature, Nature, vol. 534(7608), pages 575-578, June.
    7. Mamunur Rashid & Michiel van der Horst & Thomas Mentzel & Francesca Butera & Ingrid Ferreira & Alena Pance & Arno Rütten & Bostjan Luzar & Zlatko Marusic & Nicolas de Saint Aubain & Jennifer S. Ko & , 2019. "ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    8. Shanshan Zou & Jiarui Li & Huabang Zhou & Christian Frech & Xiaolan Jiang & Jeffrey S. C. Chu & Xinyin Zhao & Yuqiong Li & Qiaomei Li & Hui Wang & Jingyi Hu & Guanyi Kong & Mengchao Wu & Chuanfan Ding, 2014. "Mutational landscape of intrahepatic cholangiocarcinoma," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
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