IDH1R132 mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain

Giselle Y. Lopez, Zachary J. Reitman, David Solomon, Todd Waldman, Darell D. Bigner, Roger E. McLendon, Steven A. Rosenberg, Yardena Samuels, Hai Yan

Research output: Contribution to journalArticlepeer-review

Abstract

Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP. +. to NADPH). IDH1/2 were recently identified as mutated in a large percentage of progressive gliomas. These mutations occur at IDH1R132 or the homologous IDH2R172. Melanomas share some genetic features with IDH1/2-mutated gliomas, such as frequent TP53 mutation. We sought to test whether melanoma is associated with IDH1/2 mutations. Seventy-eight human melanoma samples were analyzed for IDH1R132 and IDH2R172 mutation status. A somatic, heterozygous IDH1 c.C394T (p.R132C) mutation was identified in one human melanoma metastasis to the lung. Having identified this mutation in one metastasis, we sought to test the hypothesis that certain selective pressures in the brain environment may specifically favor the cell growth or survival of tumor cells with mutations in IDH1/2, regardless of primary tumor site. To address this, we analyzed IDH1R132 and IDH2R172 mutation status 53 metastatic brain tumors, including nine melanoma metastases. Results revealed no mutations in any samples. This lack of mutations would suggest that mutations in IDH1R132 or IDH2R172 may be necessary for the formation of tumors in a cell-lineage dependent manner, with a particularly strong selective pressure for mutations in progressive gliomas; this also suggests the lack of a particular selective pressure for growth in brain tissue in general. Studies on the cell-lineages of tumors with IDH1/2 mutations may help clarify the role of these mutations in the development of brain tumors.

Original languageEnglish (US)
Pages (from-to)585-587
Number of pages3
JournalBiochemical and Biophysical Research Communications
Volume398
Issue number3
DOIs
StatePublished - Jul 1 2010

Keywords

  • Brain tumors metastases
  • Isocitrate dehydrogenase 1
  • Isocitrate dehydrogenase 2
  • Melanoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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