Role of Genetics in Treating Low-grade Glioma

Significant gaps exist in our understanding of the causes and clinical management of glioma. One of the biggest gaps is how best to manage low grade (World Health Organization (WHO) grade II) glioma patients. Low grade glioma is a uniformly fatal disease of young adults (mean age 41 years) with survival averaging approximately 7 years. Although low grade glioma patients have better survival than patients with high grade (WHO grade III/IV) glioma, all low grade gliomas eventually progress to high grade glioma and death. Data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute suggest that for the majority of low grade glioma patients, overall survival has not significantly improved over the past three decades, highlighting the need for intensified study of this tumor.

Newly published research suggests that historically utilized clinical variables are not sufficient (and are likely inferior) prognostic and predictive indicators relative to information provided by recently discovered tumor markers (e.g..1p/19q deletion and IDH1/2 mutation status), tumor expression profiles (e.g. the Proneural Profile) and/or constitutive genotype . Discovery of such tumor and constitutive variation may identify variables needed to improve randomization in clinical trials as well as patients more sensitive to current treatments and targets for improved treatment in the future. This manuscript reports on survival trends for patients diagnosed with low grade glioma within the United States from 1973–2011 and reviews the emerging role of tumor and constitutive genetics in refining risk stratification, defining targeted therapy, and improving survival for this group of relatively young patients.