MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma.
MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma.
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DOI：
10.1038/ncomms15770
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发表时间：
2017-06-08
影响因子：
16.6
通讯作者：
Kim WY
中科院分区：
文献类型：
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作者：
Bailey ST;Smith AM;Kardos J;Wobker SE;Wilson HL;Krishnan B;Saito R;Lee HJ;Zhang J;Eaton SC;Williams LA;Manocha U;Peters DJ;Pan X;Carroll TJ;Felsher DW;Walter V;Zhang Q;Parker JS;Yeh JJ;Moffitt RA;Leung JY;Kim WY
肾癌是一种常见的侵袭性恶性肿瘤，其组织发生机制尚不完全清楚，并且对细胞毒化疗具有很大的抵抗力。我们提出了两种小鼠肾癌模型，其概括了在人类乳头状（pRCC）和透明细胞RCC（ccRCC）中发现的基因组改变，这是最常见的RCC亚型。MYC活化导致高度渗透性pRCC肿瘤（MYC），而MYC活化，当与Vhl和Cdkn 2a（Ink 4a/Arf）缺失（Vim）组合时，产生接近人ccRCC的肾肿瘤。小鼠肿瘤的RNAseq证明MYC肿瘤类似于2型pRCC，已知2型pRCC具有MYC活化。此外，Vim肿瘤更接近地模拟人类ccRCC。基于它们的高转移率、短潜伏期和组织学逼真性，这些乳头状和透明细胞RCC模型将对肾癌研究领域做出重大贡献。肾细胞癌（Renal cell carcinoma，RCC）是一种常见的恶性肿瘤.在这里，作者产生了两种最常见的RCC亚型的小鼠模型：通过MYC活化的人乳头状RCC和通过MYC活化结合Vhl和Cdkn 2a缺失的透明细胞RCC。
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.