Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Nat Commun. 2017 Jun 8;8:15770. 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.
肾细胞癌是一种常见且侵袭性的恶性肿瘤，其组织发生机制尚未完全阐明，并且对细胞毒性化疗有很大的抗性。我们提出了两种能够重现人类乳头状肾细胞癌（pRCC）和透明细胞肾细胞癌（ccRCC）中发现的基因组改变的肾癌小鼠模型，这两种肾癌是最常见的肾癌亚型。MYC 的激活导致高穿透性的 pRCC 肿瘤（MYC），而当 MYC 激活与 Vhl 和 Cdkn2a（Ink4a/Arf）缺失（VIM）结合时，会产生接近人类 ccRCC 的肾脏肿瘤。对小鼠肿瘤的 RNAseq 分析表明，MYC 肿瘤类似于已知存在 MYC 激活的 2 型 pRCC。此外，VIM 肿瘤更类似于人类 ccRCC。基于其高穿透性、短潜伏期和组织学保真度，这些乳头状和透明细胞肾细胞癌的模型应该是对肾癌研究领域的重要贡献。
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