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Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma

Gerben Duns1, Eva van den Berg, Inge van Duivenbode

  • 1Departments of Genetics and Pathology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.

Cancer Research
|May 27, 2010
PubMed

Insights

Researchers identified the SETD2 gene as frequently inactivated in sporadic clear cell renal cell carcinoma (cRCC). Loss of SETD2 function impacts H3K36me3 levels, contributing to cRCC development.

Area of Science:

  • Oncology
  • Genetics
  • Epigenetics

Background:

  • Sporadic clear cell renal cell carcinoma (cRCC) frequently exhibits genetic alterations on chromosome 3p.
  • A specific hotspot for copy number loss is located in the 3p21 region.

Purpose of the Study:

  • To identify biallelically inactivated genes within the 3p21 region in cRCC cell lines.
  • To investigate the role of SETD2 in the pathogenesis of cRCC.

Main Methods:

  • Utilized gene identification by nonsense-mediated mRNA decay inhibition in 10 cRCC cell lines with 3p21 copy number loss.
  • Analyzed histone H3 trimethylation at lysine 36 (H3K36me3) levels.
  • Screened primary cRCC tumor samples for SETD2 mutations.

Main Results:

  • Identified inactivation of the histone methyltransferase gene SETD2 (3p21.31) as a common event in cRCC cells.
  • Observed loss or decreased H3K36me3 in 7 out of 10 cRCC cell lines, consistent with SETD2's function.
  • Found missense mutations in SETD2 in 2 out of 10 primary cRCC tumors.

Conclusions:

  • Loss of SETD2 function is implicated in the development of sporadic clear cell renal cell carcinoma.
  • SETD2 inactivation and its impact on H3K36me3 represent a significant pathway in cRCC tumorigenesis.

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