Methylation and transcription patterns are distinct in IDH mutant gliomas compared to other IDH mutant cancers

Dusten Unruh, Makda Zewde, Adam Buss, Michael R. Drumm, Anh N. Tran, Denise M. Scholtens, Craig Horbinski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Mutations in isocitrate dehydrogenases 1 and 2 (IDHmut) are present in a variety of cancers, including glioma, acute myeloid leukemia (AML), melanoma, and cholangiocarcinoma. These mutations promote hypermethylation, yet it is only a favorable prognostic marker in glioma, for reasons that are unclear. We hypothesized that the patterns of DNA methylation, and transcriptome profiles, would vary among IDHmut cancers, especially gliomas. Using Illumina 450K and RNA-Seq data from The Cancer Genome Atlas, we show that of 365,092 analyzed CpG sites, 70,591 (19%) were hypermethylated in IDHmut gliomas compared to wild-type (IDHwt) gliomas, and only 3%, 2%, and 4% of CpG sites were hypermethylated in IDHmut AML, melanoma, and cholangiocarcinoma, relative to each of their IDHwt counterparts. Transcriptome differences showed pro-malignant genes that appear to be unique to IDHmut gliomas. However, genes involved in differentiation and immune response were suppressed in all IDHmut cancers. Additionally, IDHmut caused a greater degree of hypermethylation in undifferentiated neural progenitor cells than in mature astrocytes. These data suggest that the extent and targets of IDHmut-induced genomic hypermethylation vary greatly according to the cellular context and may help explain why IDHmut is only a favorable prognostic marker in gliomas.

Original languageEnglish (US)
Article number8946
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General

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