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

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 Manocha, Dorien J. Peters, Xinchao Pan, Thomas J. Carroll, Dean W. Felsher, Vonn Walter, Qing Zhang, Joel S. Parker, Jen Jen Yeh, Richard A. Moffitt, Janet Y. Leung () and William Y. Kim ()
Additional contact information
Sean T. Bailey: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Aleisha M. Smith: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Jordan Kardos: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Sara E. Wobker: Lineberger Comprehensive Cancer Center, 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
Samuel C. Eaton: University of North Carolina at Chapel Hill
Lindsay A. Williams: Lineberger Comprehensive Cancer Center, 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
Joel S. Parker: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Jen Jen Yeh: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Richard A. Moffitt: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Janet Y. Leung: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
William Y. Kim: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15770

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