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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

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The epigenetic landscape of clear-cell renal cell carcinoma

Katarzyna Kluzek1, Hans A Bluyssen1, Joanna Wesoly1

  • 1Department of Human Molecular Genetics, Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznan, Umultowska 89, 61-614 Poznan, Poland.

Journal of Kidney Cancer and VHL
|March 23, 2017
PubMed

Insights

Epigenetic alterations, particularly in chromosome 3p genes like PBRM1, SETD2, and BAP1, are crucial in clear cell renal cell carcinoma (ccRCC) development. These changes in chromatin regulation offer potential for new diagnostic and therapeutic approaches in ccRCC.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the predominant kidney tumor subtype.
  • Epigenetics, especially DNA methylation and gene mutations, plays a significant role in ccRCC pathogenesis.
  • Alterations in chromatin regulatory proteins are frequently observed in ccRCC.

Purpose of the Study:

  • To review recent advancements in understanding the deregulation of chromatin machinery in ccRCC.
  • To highlight the significance of epigenetic modifications in ccRCC.
  • To explore the potential of ccRCC-specific epigenetic alterations as biomarkers and therapeutic targets.

Main Methods:

  • Large-scale methylation and sequencing analyses were employed.
  • Identification of frequently inactivated genes via promoter methylation.
  • Recurrent mutation analysis in chromatin regulatory genes.

Main Results:

  • Genes such as PBRM1, SETD2, and BAP1 on chromosome 3p, near the VHL gene, are frequently altered.
  • Inactivation of these 3p genes occurs in over 80% of ccRCC cases.
  • The proteins encoded by these genes are involved in cooperative histone H3 modifications.

Conclusions:

  • Alterations in chromosome 3p are fundamental to ccRCC pathogenesis.
  • Epigenetic modifications in ccRCC present opportunities for novel diagnostic and prognostic biomarkers.
  • These findings may pave the way for new therapeutic strategies targeting ccRCC.

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