Genomic Analysis Identifies New Prognostic Molecular Subtypes of Diffuse Lower-Grade Gliomas


The Cancer Genome Atlas Research Network characterized low-grade gliomas through a genome-wide analysis of 293 previously-untreated adult lower-grade glioma: oligodendrogliomas (n=116), astrocytomas (n=100), and oligoastrocytomas (n=77).  Overall, data from DNA copy number, RNA, and DNA methylation status demonstrated three distinct and prognostic subtypes of low-grade gliomas based upon IDH, 1p/19q/ and TP53-status.  Importantly, these molecular signatures were more accurate than histologic class when correlated with clinical outcome.  The most favorable clinical outcomes associated with lower-grade gliomas harboring an IDH mutation and 1p/19q co-deletion. These patients also commonly harbored CIC, FUBP1, NOTCH1 and the TERT promoter gene mutations.  Interestingly, the majority of low-grade gliomas without an IDH mutation had clinical behavior strikingly similar to primary glioblastoma.  These findings (New England Journal of Medicine, June 2015) set the stage for transitioning to molecular marker-based glioma classification.

Nader Sanai, MD
Phoenix, AZ