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MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma

Author

Listed:
  • Sean T. Bailey

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Aleisha M. Smith

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Jordan Kardos

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Sara E. Wobker

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Harper L. Wilson

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)

  • Bhavani Krishnan

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)

  • Ryoichi Saito

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)

  • Hyo Jin Lee

    (Chungnam National University School of Medicine)

  • Jing Zhang

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Samuel C. Eaton

    (University of North Carolina at Chapel Hill)

  • Lindsay A. Williams

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    Gillings School of Global Public Health, University of North Carolina at Chapel Hill)

  • Ujjawal Manocha

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill)

  • Dorien J. Peters

    (Leiden University Medical Center)

  • Xinchao Pan

    (UT Southwestern Medical Center)

  • Thomas J. Carroll

    (UT Southwestern Medical Center)

  • Dean W. Felsher

    (Stanford University School of Medicine)

  • Vonn Walter

    (Penn State Milton S. Hershey College of Medicine)

  • Qing Zhang

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Joel S. Parker

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Jen Jen Yeh

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Richard A. Moffitt

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Janet Y. Leung

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • William Y. Kim

    (Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

Abstract

Renal carcinoma is a common and aggressive malignancy whose histopathogenesis is incompletely understood and that is largely resistant to cytotoxic chemotherapy. We present two mouse models of kidney cancer that recapitulate the genomic alterations found in human papillary (pRCC) and clear cell RCC (ccRCC), the most common RCC subtypes. MYC activation results in highly penetrant pRCC tumours (MYC), while MYC activation, when combined with Vhl and Cdkn2a (Ink4a/Arf) deletion (VIM), produce kidney tumours that approximate human ccRCC. RNAseq of the mouse tumours demonstrate that MYC tumours resemble Type 2 pRCC, which are known to harbour MYC activation. Furthermore, VIM tumours more closely simulate human ccRCC. Based on their high penetrance, short latency, and histologic fidelity, these models of papillary and clear cell RCC should be significant contributions to the field of kidney cancer research.

Suggested Citation

  • Sean T. Bailey & Aleisha M. Smith & Jordan Kardos & Sara E. Wobker & Harper L. Wilson & Bhavani Krishnan & Ryoichi Saito & Hyo Jin Lee & Jing Zhang & Samuel C. Eaton & Lindsay A. Williams & Ujjawal Ma, 2017. "MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma," Nature Communications, Nature, vol. 8(1), pages 1-12, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15770
    DOI: 10.1038/ncomms15770
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    Cited by:

    1. Joyce V. Lee & Filomena Housley & Christina Yau & Rachel Nakagawa & Juliane Winkler & Johanna M. Anttila & Pauliina M. Munne & Mariel Savelius & Kathleen E. Houlahan & Daniel Mark & Golzar Hemmati & G, 2022. "Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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