IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain.

Journal Article (Journal Article)

Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-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 IDH1(R132) or the homologous IDH2(R172). 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 IDH1(R132) and IDH2(R172) 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 IDH1(R132) and IDH2(R172) 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 IDH1(R132) or IDH2(R172) 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.

Full Text

Duke Authors

Cited Authors

  • Lopez, GY; Reitman, ZJ; Solomon, D; Waldman, T; Bigner, DD; McLendon, RE; Rosenberg, SA; Samuels, Y; Yan, H

Published Date

  • July 30, 2010

Published In

Volume / Issue

  • 398 / 3

Start / End Page

  • 585 - 587

PubMed ID

  • 20603105

Pubmed Central ID

  • PMC2987603

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2010.06.125


  • eng

Conference Location

  • United States