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DNA hypermethylation in intrahepatic cholangiocarcinomas and glioblastomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32286 | GEO | 2012/06/10

SECONDARY ACCESSION(S): PRJNA146357

REPOSITORIES: GEO

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DNA hypermethylation in intrahepatic cholangiocarcinomas and glioblastomas

Project description:This SuperSeries is composed of the following subset Series: GSE32079: Mutations in IDH1 and IDH2 are associated with DNA hypermethylation in intrahepatic cholangiocarcinomas GSE32283: Mutations in IDH1 are associated with DNA hypermethylation in glioblastomas Refer to individual Series

2012-06-09 | E-GEOD-32286 | biostudies-arrayexpress

Mutations in isocitrate dehydrogenase 1 and 2 occur frequently in intrahepatic cholangiocarcinomas and share hypermethylation targets with glioblastomas.

Project description:Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine and higher 5-methylcytosine levels, as well as increased dimethylation of histone H3 lysine 79 (H3K79). Mutations in IDH1 or IDH2 were associated with longer overall survival (P=0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (P=0.021). IDH1 and IDH2 mutations were significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors.

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Mutations in IDH1 and IDH2 are associated with DNA hypermethylation in intrahepatic cholangiocarcinomas

Project description:We compared the DNA methylation profiles of 12 intrahepatic cholangiocarcinomas harboring mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, with 28 intrahepatic cholangiocarcinomas without these mutations. We profiled these samples with the Illumina HumanMethylation450 BeadChip, and characterized over 2,000 genes that were hypermethylated in tumors with mutations in IDH1 or IDH2.

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Tumor hypoxia causes DNA hypermethylation by reducing TET activity

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