Genetics in glioma: lessons learned from genome-wide association studies

The purpose of this review is to describe the recent knowledge gathered from the identification of seven genomic regions that have been linked to the risk of developing malignant glioma.

The recent novel discoveries in fine mapping and genotype-phenotype studies will be highlighted. Through imputation and next-generation sequencing a novel genetic variant, rs55705857, with a strong association at 8q24 has been discovered and validated in two studies. This locus is specifically associated with IDH1-mutated and IDH2-mutated tumors and oligodendroglial tumors, albeit the specific mechanism of tumor development is not understood. The genetic variants associated with the risk of glioma in the EGFR gene have also been associated with specific somatic aberrations, including loss at the CDKN2A/B locus and allele specific loss of EGFR in the tumors. A specific TP53 low frequency variant has also been associated with glioma risk and validated in a separate data set. The genetic risk in the telomere regulating genes TERT and RTEL appear to be associated with higher grade tumors without IDH mutations.

The link of genetic loci to specific tumor subtypes may have relevance for understanding glioma biology, and for developing new diagnostic tools and targeted therapy for glioma.