| Autor: |
Whitehall, VLJ, Dumenil, TD, McKeone, DM, Bond, CE, Bettington, ML, Buttenshaw, RL, Bowdler, L, Montgomery, GW, Wockner, LF, Leggett, BA |
| Zdroj: |
Epigenetics; November 2014, Vol. 9 Issue: 11 p1454-1460, 7p |
| Abstrakt: |
The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAFmutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1(IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1alteration as a potential cause of CIMP in colorectal cancer. The IDH1mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1mutation was detected in 4/166 cancers. All IDH1mutations were in CIMP cancers that were BRAFmutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1mutation appears to cause CIMP in a small proportion of BRAFmutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
