The SWI/SNF Protein PBRM1 Restrains VHL-Loss-Driven Clear Cell Renal Cell Carcinoma Academic Article uri icon

Overview

MeSH Major

  • Cell Tracking
  • Neoplasms
  • Radiopharmaceuticals
  • T-Lymphocytes
  • Tomography, Emission-Computed

abstract

  • PBRM1 is the second most commonly mutated gene after VHL in clear cell renal cell carcinoma (ccRCC). However, the biological consequences of PBRM1 mutations for kidney tumorigenesis are unknown. Here, we find that kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PBRM1 loss amplified the transcriptional outputs of HIF1 and STAT3 incurred by Vhl deficiency. Analysis of mouse and human ccRCC revealed convergence on mTOR activation, representing the third driver event after genetic inactivation of VHL and PBRM1. Our study reports a physiological preclinical ccRCC mouse model that recapitulates somatic mutations in human ccRCC and provides mechanistic and therapeutic insights into PBRM1 mutated subtypes of human ccRCC.

publication date

  • March 21, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5431084

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2017.02.074

PubMed ID

  • 28329682

Additional Document Info

start page

  • 2893

end page

  • 2906

volume

  • 18

number

  • 12