Most patients diagnosed with brain tumors or gliomas only live about 15 months after the diagnosis, but a few patients beat the odds, living several more years. Researchers with The Cancer Genome Atlas (TCGA) now say that they can tell which patients will have better outcomes by looking at their DNA methylation. Those with a certain, stable pattern of hypermethylation (“glioma-CpG island methylator phenotype”; G-CIMP) have better clinical outcomes than patients who don’t have the mods.
The researchers used methylation assays and microarrays to study DNA methylation in 272 TCGA brain tumor samples. When the dust settled, and they clustered the data, they saw an obvious subgroup of 24 samples in which a specific subset of genes was hypermethylated. These G-CIMP+ tumors expressed several proneural genes and turned out to be very interesting.
- The scientists found that a G-CIMP+ status meant patients had much higher survival rates.
- G-CIMP+ was tightly correlated with IDH1 mutations, and these tumors had a distinct copy-number variation profile.
- 263 genes were both down-regulated and hypermethylated in G-CIMP+ tumors compared with G-CIMP– ones.
- A meta-analysis confirmed the association between the 263 gene set with low-grade tumors and high-grade tumors with good outcomes and younger ages at diagnosis.
- The team used the methylation status of a panel of 8 genes to validate the results.
- They pulled out G-CIMP+ tumors from an independent sample set at the same rate as the TCGA set, and these also had IDH1 mutations.
Find the nitty-gritty detils at Cancer Cell, May 18, 2010.