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Clonal architectures predict clinical outcome in clear cell renal cell carcinoma

Author

Listed:
  • Yi Huang

    (Xi’an Jiaotong University
    Geneplus-Beijing)

  • Jiayin Wang

    (Xi’an Jiaotong University)

  • Peilin Jia

    (The University of Texas Health Science Center at Houston)

  • Xiangchun Li

    (Tianjin Medical University Cancer Institute and Hospital)

  • Guangsheng Pei

    (The University of Texas Health Science Center at Houston)

  • Changxi Wang

    (Geneplus-Beijing)

  • Xiaodong Fang

    (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine)

  • Zhongming Zhao

    (The University of Texas Health Science Center at Houston)

  • Zhiming Cai

    (The Third Affiliated Hospital of Shenzhen University)

  • Xin Yi

    (Geneplus-Beijing)

  • Song Wu

    (The Third Affiliated Hospital of Shenzhen University)

  • Baifeng Zhang

    (Geneplus-Beijing)

Abstract

The genetic landscape of clear cell renal cell carcinoma (ccRCC) had been investigated extensively but its evolution patterns remained unclear. Here we analyze the clonal architectures of 473 patients from three different populations. We find that the mutational signatures vary substantially across different populations and evolution stages. The evolution patterns of ccRCC have great inter-patient heterogeneities, with del(3p) being regarded as the common earliest event followed by three early departure points: VHL and PBRM1 mutations, del(14q) and other somatic copy number alterations (SCNAs) including amp(7), del(1p) and del(6q). We identify three prognostic subtypes of ccRCC with distinct clonal architectures and immune infiltrates: long-lived patients, enriched with VHL but depleted of BAP1 mutations, have high levels of Th17 and CD8+ T cells while short-lived patients with high burden of SCNAs have high levels of Tregs and Th2 cells, highlighting the importance of evaluating evolution patterns in the clinical management of ccRCC.

Suggested Citation

  • Yi Huang & Jiayin Wang & Peilin Jia & Xiangchun Li & Guangsheng Pei & Changxi Wang & Xiaodong Fang & Zhongming Zhao & Zhiming Cai & Xin Yi & Song Wu & Baifeng Zhang, 2019. "Clonal architectures predict clinical outcome in clear cell renal cell carcinoma," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09241-7
    DOI: 10.1038/s41467-019-09241-7
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    Cited by:

    1. Akihiko Fukagawa & Natsuko Hama & Yasushi Totoki & Hiromi Nakamura & Yasuhito Arai & Mihoko Saito-Adachi & Akiko Maeshima & Yoshiyuki Matsui & Shinichi Yachida & Tetsuo Ushiku & Tatsuhiro Shibata, 2023. "Genomic and epigenomic integrative subtypes of renal cell carcinoma in a Japanese cohort," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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