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Updated: Feb 19, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

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Insights into Epigenetic Remodeling in VHL-Deficient Clear Cell Renal Cell Carcinoma

Christopher J Ricketts1, W Marston Linehan2

  • 1Urologic Oncology Branch, Center for Cancer Research, NCI, Bethesda, Maryland.

Cancer Discovery
|November 4, 2017
PubMed

Insights

Loss of the von Hippel-Lindau (VHL) gene in clear cell renal cell carcinoma (ccRCC) alters chromatin. This study reveals VHL loss impacts gene promoters and enhancers, offering new therapeutic targets for advanced ccRCC.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) is strongly associated with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene.
  • Therapies for advanced ccRCC currently target downstream consequences of VHL loss, such as the hypoxia-inducible factor (HIF) pathway.

Purpose of the Study:

  • To investigate the role of VHL loss in chromatin alterations at gene regulatory elements in ccRCC.
  • To identify potential novel therapeutic targets beyond HIF pathway activation.

Main Methods:

  • Analysis of chromatin accessibility and modifications in ccRCC models with VHL loss.
  • Investigation of both HIF-dependent and HIF-independent mechanisms of VHL's effect on chromatin.

Main Results:

  • VHL loss induces widespread chromatin alterations at both gene promoters and enhancers/superenhancers.
  • These chromatin changes occur through both HIF-dependent and HIF-independent mechanisms.
  • Identified specific chromatin alterations that could be targeted therapeutically.

Conclusions:

  • VHL loss profoundly impacts the ccRCC epigenome, affecting gene regulation beyond the HIF pathway.
  • These VHL-dependent chromatin alterations represent promising new therapeutic targets for advanced ccRCC.

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