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Updated: Mar 1, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma
Sean T Bailey1,2, Aleisha M Smith1,2, Jordan Kardos1,2
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
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.
Insights
Researchers developed two mouse models for kidney cancer, mimicking human papillary and clear cell renal carcinoma (RCC). These models, driven by MYC activation and Vhl/Cdkn2a deletion, offer valuable tools for advancing renal carcinoma research.
Area of Science:
- Oncology
- Genetics
- Animal Models
Background:
- Renal carcinoma (kidney cancer) is a prevalent and aggressive malignancy.
- Its origins and resistance to chemotherapy are not fully understood.
Purpose of the Study:
- To develop and characterize novel mouse models for renal carcinoma.
- To mimic the genomic alterations observed in human papillary (pRCC) and clear cell (ccRCC) subtypes.
Main Methods:
- Generation of mouse models with specific genetic alterations (MYC activation, Vhl and Cdkn2a deletion).
- Histological analysis and RNA sequencing (RNAseq) of induced kidney tumors.
- Comparison of mouse tumor characteristics with human RCC subtypes.
Main Results:
- MYC activation in mice led to highly penetrant papillary renal carcinoma (pRCC) resembling Type 2 pRCC.
- Combined MYC activation with Vhl and Cdkn2a deletion (VIM model) produced kidney tumors closely simulating human clear cell renal carcinoma (ccRCC).
- Both models exhibit high penetrance, short latency, and histologic fidelity.
Conclusions:
- The developed mouse models accurately recapitulate key genomic alterations and histological features of human pRCC and ccRCC.
- These models represent significant contributions to kidney cancer research, facilitating further studies into pathogenesis and treatment.
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