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Apr 16, 2010

Researchers Find Hypermethylation in Glioblastoma Indicates Earlier Disease Onset but Improved Outcomes

  • A group of researchers have identified patterns of hypermethylation at a large number of genetic loci in a subgroup of glioblastoma patients who tend to be relatively young at the time of diagnosis and experience improved outcome.

    The team comprised scientists from The Cancer Genome Atlas Consortium (TCGA) led by a team from the University of Southern California and The University of Texas M. D. Anderson Cancer Center. Their results are published in Cancer Cell in a paper titled “Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma.”

    To investigate the potential role of methylation in glioblastoma, the researchers profiled promoter DNA methylation alterations in 272 glioblastoma tumors from TCGA.

    Their results showed that 24 of these glioblastomas were methylated at CpG islands of the defined gene set. This indicated the existence of what they termed a glioma-CpG island methylator phenotype (G-CIMP). The findings were validated in a set of non-TCGA glioblastomas and low-grade gliomas.

    Of the 24 methylated tumors, 21 were in the proneural group. Moreover, among grade IV glioblastoma patients, the median survival for the CIMP-positive group was 150 weeks compared with 42 weeks for those negative for the epigenetic signature. CIMP-positivity was also more common in low-to-intermediate grade tumors. There was a 10-fold increase in methylation in grade II tumors compared with grade IV glioblastomas.

    “G-CIMP tumors belong to the proneural subgroup, are more prevalent among lower-grade gliomas, display distinct copy-number alterations, and are tightly associated with IDH1 somatic mutations,” the researchers conclude. “Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome.”

    The researchers also suggest that CpG island biomarkers could help identify which low- or intermediatie-grade glioma patients have relatively good or poor prognoses.


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