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Functional and Topographic Effects on DNA Methylation Across IDH1/2 Mutant Cancers

ABSTRACT: Background: IDH1/2 mutations are present in cancer arising from various tissues; however, common and disease specific effects on DNA methylation across IDH mutant cancers remain unknown. Results: We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia (AML), oligodendroglioma, astrocytoma, breast carcinoma, sinonasal undifferentiated carcinoma (SNUC) and cholangiocarcinoma. We show that only a small fraction of differentially methylated probes is disease specific and that hypermethylation affects predominantly gene bodies and enhancers while gene promoters in IDH1/2 mutant cancers remain profoundly unmethylated. Commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We also show that some chromosomes and chromosomal regions are more affected by IDH mutation. In particular we show that regions of dense heterochromatin on several chromosomes do not appear to be affected by IDH mutation induced hypermethylation. Conclusions: We show that there are gene region and chromosome specific areas that are preferentially affected or spared by changes in DNA methylation across IDH mutant cancers. This suggests that while IDH mutation causes the same biochemical change in all cancers, the effect may vary in tissue specific fashion. Hypomethylation of enhancers associated with cell differentiation may mediate lack of differentiation in IDH1/2mutant cancers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124617 | GEO | 2020/01/15

REPOSITORIES: GEO

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