Assessing glioma by histomorphology and grade offers little predictive value when it comes to the later development of glioblastoma, but diving into the epigenetics may uncover useful biomarkers. A research group led by Houtan Noushmehr, Professor and researcher at the Henry Ford Health System, investigated the DNA methylation profile of 200 tumors from 77 patients, which revealed biomarkers of aggressive tumor recurrence (1).
“In 2010, we defined a subset of gliomas that harbored a unique epigenetic profile, which we termed G-CIMP (glioma - CpG Island Methylator Phenotype) (2). It was later shown that isocitrate dehydrogenase mutations can initiate this methylator phenotype, and our recent findings may provide additional diagnostic tools to aid oncologists in determining proper therapeutic avenues,” says Noushmehr. Looking at the DNA methylation of high- and low-G-CIMP tumors, then identifying the intra-heterogeneity within primary high-G-CIMP tumors – which often carry worse prognoses – allowed the team to uncover predictive biomarker signatures comprising seven hypomethylated CpG sites in the tumors. “The biomarkers could potentially be used as an additional screening method during pathological review. Currently, histological and molecular features are evaluated during normal standard of care for patients with evidence of brain cancer,” he says. “Our markers have the potential be included in this initial standard of care. However, further studies are needed to confirm and validate our discovery; specifically, a pre-clinical trial would need to be performed.” Looking forward, the investigators hope to use bioinformatics and advanced sequencing techniques to discover which genomic components play an important role in glioma tumor development. And they will continue to explore the intricacies of the relationship between the epigenome and genome within glioma subtypes. Noushmehr adds, “We are also working closely with oncologists, neuropathologists and neurosurgeons to hopefully translate some of our initial work into clinical applications.”
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References
- CF de Souza et al., “A distinct shift in a subset of glioma CpG island methylator phenotypes during tumor recurrence”, Cell Rep, 23, 637 – 651 (2018). PMID: 29642018. H Noushmehr et al., “Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma”, Cancer Cell, 17, 510 – 522 (2010). PMID: 20399149.
