Genomics

Dataset Information

298

Induction of sarcomas by mutant IDH2


ABSTRACT: More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions. Regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification. In murine 10T1/2 mesenchymal 20 progenitor cells, expression of mutant IDH2 led to DNA hypermethylation and an impairment in differentiation that could be reversed by treatment with DNA-hypomethylating agents. Introduction of mutant IDH2 also induced loss of contact inhibition and generated undifferentiated sarcomas in vivo. The oncogenic potential of mutant IDH2 correlated with the ability to produce 2-hydroxyglutarate. Together, these data demonstrate that neomorphic IDH2 mutations can be oncogenic in mesenchymal cells.. RRBS sequencing of (1) IDH wild type and mutant human chondrosarcomas, (2) isogenic cell lines expressing wild-type or mutant IDH.

ORGANISM(S): Homo sapiens  

SUBMITTER: Jiangbin Ye   Khedoudja Nafa  Meera Hameed  John H Healey  Andrew M Intlekofer  Scott W Lowe  Chong Chen  Raya Khanin  Gary K Schwartz  Patrick S Ward  Ari Melnick  Chao Lu  Narasimhan P Agaram  Sriram Venneti  Christopher E Mason  Justin R Cross  Raymond G DeMatteo  Fang Fang  Craig B Thompson  Altuna Akalin 

PROVIDER: E-GEOD-50539 | ArrayExpress | 2013-10-21

SECONDARY ACCESSION(S): SRP029519GSE50539PRJNA217989

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications


More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions. Regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification. In murine 10  ...[more]

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