文章基本信息

标题：Methylation and transcription patterns are distinct in IDH mutant gliomas compared to other IDH mutant cancers
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作者：Dusten Unruh ; Makda Zewde ; Adam Buss 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-11
DOI：10.1038/s41598-019-45346-1
出版社：Springer Nature
摘要：Mutations in isocitrate dehydrogenases 1 and 2 (IDH mut ) 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 IDH mut 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 IDH mut gliomas compared to wild-type (IDH wt ) gliomas, and only 3%, 2%, and 4% of CpG sites were hypermethylated in IDH mut AML, melanoma, and cholangiocarcinoma, relative to each of their IDH wt counterparts. Transcriptome differences showed pro-malignant genes that appear to be unique to IDH mut gliomas. However, genes involved in differentiation and immune response were suppressed in all IDH mut cancers. Additionally, IDH mut caused a greater degree of hypermethylation in undifferentiated neural progenitor cells than in mature astrocytes. These data suggest that the extent and targets of IDH mut -induced genomic hypermethylation vary greatly according to the cellular context and may help explain why IDH mut is only a favorable prognostic marker in gliomas.