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 YehRichard A. Moffitt, Janet Y. Leung, William Y. Kim

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Article number15770
JournalNature communications
Volume8
DOIs
StatePublished - Jun 8 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Bailey, S. T., Smith, A. M., Kardos, J., Wobker, S. E., Wilson, H. L., Krishnan, B., Saito, R., Lee, H. J., Zhang, J., Eaton, S. C., Williams, L. A., Manocha, U., Peters, D. J., Pan, X., Carroll, T. J., Felsher, D. W., Walter, V., Zhang, Q., Parker, J. S., ... Kim, W. Y. (2017). MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma. Nature communications, 8, [15770]. https://doi.org/10.1038/ncomms15770