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首页 > 医学词汇大全 > von Hippel-Lindau Gene
von Hippel-Lindau Gene

肾内泌尿

关键词肾内泌尿 临床研究术语 基因

词汇介绍

拓展阅读

解析

von Hippel-Lindau 

释    义   n. VHL基因

例    句  von Hippel-Lindau disease is a heritable multisystem cancer syndrome that is associated with a germline mutation of the VHL tumour suppressor gene on the short arm of chromosome 3.逢希伯-林道病是一种遗传性多系统癌症综合征,与3号染色体短臂VHL肿瘤抑制基因的种系突变有关。

概述

  肾癌是泌尿外科常见的肿瘤,发病率占成人全部恶性肿瘤的2%-3%。肾癌的总体疗效并不满意,深入了解肾癌的发病机制并在此基础上探索早期诊断和治疗方法是非常必要的。肾癌的发病涉及多种基因,其中VHL基因与肾癌的关系最为密切。VHL基因得名于VHL病(Yon Hippel-Lindau’s disease),VHL病为一种常染色体显性遗传的家族性肿瘤综合征,涉及多个系统病变,包括肾癌,中枢神经系统和视网膜的成血管细胞瘤、肾上腺嗜铬细胞瘤、肾、胰腺和附睾囊

Loss of PBRM1 Rescues VHL Dependent Replication Stress to Promote Renal Carcinogenesis复制标题

PBRM1的丢失挽救了VHL依赖性复制应激,促进了肾癌的发生。

发表时间:2017-12-11

影响因子:12.1

作者: Nat Commun

期刊:Espana-Agusti J

Inactivation of the VHL (Von Hippel Lindau) tumour suppressor has long been recognised as necessary for the pathogenesis of clear cell renal cancer (ccRCC); however, the molecular mechanisms underlying transformation and the requirement for additional genetic hits remain unclear. Here, we show that loss of VHL alone results in DNA replication stress and damage accumulation, effects that constrain cellular growth and transformation. By contrast, concomitant loss of the chromatin remodelling factor PBRM1 (mutated in 40% of ccRCC) rescues VHL-induced replication stress, maintaining cellular fitness and allowing proliferation. In line with these data we demonstrate that combined deletion of Vhl and Pbrm1 in the mouse kidney is sufficient for the development of fully-penetrant, multifocal carcinomas, closely mimicking human ccRCC. Our results illustrate how VHL and PBRM1 co-operate to drive renal transformation and uncover replication stress as an underlying vulnerability of all VHL mutated renal cancers that could be therapeutically exploited.

译文

长期以来,人们一直认为灭活VHL(Von Hippel Lindau)抑癌剂对于透明细胞肾癌(ccRCC)的发病机理是必不可少的。然而,转化的分子机制以及对其他基因突变的需求尚不清楚。在这里,我们表明仅VHL的丢失会导致DNA复制压力和损伤积累,这种作用会限制细胞的生长和转化。相比之下,染色质重塑因子PBRM1的伴随损失(突变为ccRCC的40%)挽救了VHL诱导的复制压力,维持了细胞的适应性并允许增殖。根据这些数据,我们证明小鼠肾脏中Vhl和Pbrm1的联合缺失足以发展为完全模仿人ccRCC的全穿透性多灶癌。我们的结果说明了VHL和PBRM1如何协同作用来驱动肾脏转化并揭示复制应激,这是所有可以治疗性利用VHL突变的肾癌的潜在脆弱性。