Gliomas are tumors that form in the astrocytes and glial cells, which support the neurons. They are currently classified by microscopic examination. Glioblastomas, the most aggressive form of brain tumor, account for 50 percent of gliomas and have a median survival time of 15 months.
The team found that 24 of 272 glioblastomas were methylated at CpG islands for the defined gene set, and termed these cases as positive for the CpG island methylator phenotype (CIMP). Subsequent experiments, Aldape said, robustly defined the subgroup by genetic mutation, gene expression pattern and clinical outcome.
Glioblastomas are grouped by several types, or signatures, of gene expression that drive the tumor. Of the 24 methylated tumors, 21 fell in the "proneural" signature in which the genes expressed are associated with neural development. The team found that patients with CpG island methylation had a median age at diagnosis of 36, compared with 59 for those without.
Two avenues to new therapies
Among grade IV glioblastoma patients, the median survival for the CIMP-positive group was 150 weeks, compared with 42 weeks for those negative for this epigenetic alteration. CIMP-positivity was more common in low- and intermediate-grade tumors, with a 10-fold increase in methylation seen in grade II tumors compared with grade IV glioblastomas.
Aldape said study results could lead to better therapies two ways. "First, this alteration could identify glioblastoma patients with outcomes similar to lower grade tumors. Second, since it is so common in lower grade tumors, it represents a new therapeutic target for these patients."
Methylation also was tightly associated with mutation in the IDHI gene in 78 percent of cases
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center