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A clearer view of the molecular complexity of clear cell renal cell carcinoma.
Annual Review of Pathology: Mechanisms of Disease ( IF 28.4 ) Pub Date : 2014-11-12 , DOI: 10.1146/annurev-pathol-012414-040306
Ian J Frew 1 , Holger Moch
Affiliation  

The von Hippel-Lindau (VHL) tumor suppressor gene is mutated as an early event in almost all cases of clear cell renal cell carcinoma (ccRCC), the most frequent form of kidney cancer. In this review we discuss recent advances in understanding how dysregulation of the many hypoxia-inducible factor α-dependent and -independent functions of the VHL tumor suppressor protein (pVHL) can contribute to tumor initiation and progression. Recent evidence showing extensive inter- and intratumoral genetic diversity has given rise to the idea that ccRCC should actually be considered as a series of molecularly related, yet distinct, diseases defined by the pattern of combinatorial genetic alterations present within the cells of the tumor. We highlight the range of genetic and epigenetic alterations that recur in ccRCC and discuss the mechanisms through which these events appear to function cooperatively with a loss of pVHL function in tumorigenesis.

中文翻译:

透明细胞肾细胞癌分子复杂性的更清晰视图。

在几乎所有的透明细胞肾细胞癌(ccRCC)病例中,von Hippel-Lindau(VHL)肿瘤抑制基因都被突变为早期事件,这是肾癌的最常见形式。在这篇综述中,我们讨论了了解VHL肿瘤抑制蛋白(pVHL)的许多低氧诱导因子α依赖性和非依赖性功能的失调如何有助于肿瘤的发生和发展的最新进展。最近的证据显示,广泛的肿瘤内和肿瘤内遗传多样性已经引起了这样的想法,即ccRCC实际上应被视为一系列分子相关但又截然不同的疾病,这些疾病是由肿瘤细胞内存在的组合遗传改变的模式所定义的。
更新日期:2019-11-01
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