Favorable prognostic impact of alterations in wild-type isocitrate dehydrogenase and promoter glioblastoma.

BACKGROUND

promoter () mutations are a biological marker of glioblastoma; however, the prognostic significance of mutational status is controversial. We evaluated this impact by retrospectively analyzing the outcomes of patients with isocitrate dehydrogenase ( and -type glioblastomas.

METHODS

Using custom next-generation sequencing, we analyzed 208 glioblastoma samples harboring wild-type .

RESULTS

mutations were detected in 143 samples (68.8%). The remaining 65 (31.2%) were -wild-type. Among the -wild-type glioblastoma samples, we observed a significant difference in median progression-free survival (18.6 and 11.4 months, respectively) and overall survival (not reached and 15.7 months, respectively) in patients with and without loss and/or mutation. Patients with -wild-type glioblastomas with loss and/or mutation were younger and had higher Karnofsky Performance Status scores than those without loss and/or mutation. We divided the patients with -wild-type into 3 clusters using unsupervised hierarchical clustering: Good ( and alterations; lack of homozygous deletion and alterations), intermediate ( alterations, homozygous deletion, lack of and alterations), and poor ( and alterations, homozygous deletion, and lack of alterations) outcomes. Kaplan-Meier survival analysis indicated that these clusters significantly correlated with the overall survival of -wild-type glioblastoma patients.

CONCLUSIONS

Here, we report that loss and/or mutation is the most useful marker for predicting favorable outcomes in patients with - and -wild-type glioblastomas. The combination of 4 genes, , , , and , is important for the molecular classification and individual prognosis of patients with - and -wild-type glioblastomas.