This tab shows an overview of the selected study/paper [more details]
Reference

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

Paper Id
COSP29455
Authors
Wang P,Dong Q,Zhang C,Kuan PF,Liu Y,Jeck WR,Andersen JB,Jiang W,Savich GL,Tan TX,Auman JT,Hoskins JM,Misher AD,Moser CD,Yourstone SM,Kim JW,Cibulskis K,Getz G,Hunt HV,Thorgeirsson SS,Roberts LR,Ye D,Guan KL,Xiong Y,Qin LX and Chiang DY
Affiliation
1] State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China [2] Molecular and Cell Biology Laboratory, Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Journal
Oncogene 2012
ISSN:1476-5594
PUBMED:22824796
Abstract
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.Oncogene advance online publication, 23 July 2012; doi:10.1038/onc.2012.315.
Paper Status
Curated
Genes Analysed
24
Mutated Samples
35
Total No. of Samples
327
This tab shows genes with mutations in the selected study/paper [more details]
Genes Samples CDS Mutation AA Mutation
This tab shows genes without mutations in the selected study/paper [more details]
Non-Mutant Genes Gene Id (COSG)
This tab shows samples without mutations in the selected study/paper [more details]
Non-Mutant Samples Sample Id (COSS)
This tab shows mutated samples in the selected study/paper [more details]
Sample Name Mutation Count
This tab shows non coding variant in the selected study/paper [more details]
Sample ID Sample Name ID NCV Annotation Zygosity Chromosome Genome start Genome stop Genome version Strand WT seq Mut seq
This tab shows the copy number variation data for this study. Only variants (classified as gain or loss) are listed. [more details]
CNV Gene Sample Position Minor Allele Copy Number Average Ploidy

1. N/A represents cases where average ploidy value is not available( mostly ICGC samples). For some TCGA samples where minor allele information is not available the average ploidy value could not be calculated.

2. For TCGA samples, Ascat algorithm is used to calculate the average ploidy.

3. For CGP samples, Picnic algorithm is used to calculate the average ploidy.

Type
This tab shows a table of count of samples having gain or loss for all genes [more details]
Gene Gain Samples Loss Samples Samples Tested
This tab shows the fusion mutations observed in this sample [more details]
Gene Sample Name Id Sample(COSS) CDS Mutation Somatic status Zygosity Validated Type