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

• Published in: Nature communications Vol. 8; no. 1; p. 15770
• Main Authors: Bailey, Sean T., Smith, Aleisha M., Kardos, Jordan, Wobker, Sara E., Wilson, Harper L., Krishnan, Bhavani, Saito, Ryoichi, Lee, Hyo Jin, Zhang, Jing, Eaton, Samuel C., Williams, Lindsay A., Manocha, Ujjawal, Peters, Dorien J., Pan, Xinchao, Carroll, Thomas J., Felsher, Dean W., Walter, Vonn, Zhang, Qing, Parker, Joel S., Yeh, Jen Jen, Moffitt, Richard A., Leung, Janet Y., Kim, William Y.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.06.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 38/39; 45/29; 45/90; 45/91; 59; 631/67/70; 64/60; 692/4028/67/589/1588/1351; 82; 82/1; 82/29; ADP-Ribosylation Factors - genetics; ADP-Ribosylation Factors - metabolism; Animals; Cancer research; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Gene Expression Regulation, Neoplastic; Genes; Genes, myc; Humanities and Social Sciences; Humans; Internal medicine; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Medical prognosis; Medical research; Medicine; Metastasis; Mice, Knockout; Mice, Transgenic; Molecular biology; multidisciplinary; Mutation; Science; Science (multidisciplinary); Tumors; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Von Hippel-Lindau Tumor Suppressor Protein - metabolism; Xenograft Model Antitumor Assays; North Carolina; United States > US
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15770

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. Renal cell carcinoma (RCC) is a common and aggressive malignancy. Here, the authors generate two mouse models of the most common RCC subtypes: the human papillary RCC through MYC activation and clear cell RCC through MYC activation combined with Vhl and Cdkn2a deletion.