P09.24 The germline mutation PIK3R1Met326Ile correlates with the levels of cysteine<->rich protein 61 and poor prognosis of glioblastoma

Despite advances in treatment, glioblastoma remains a lethal brain tumor. Efforts to identify prognostic molecular biomarkers for glioblastoma have intensified, and we previously reported that the median progression-free survival (PFS) and overall survival (OS) of patients with high levels of cysteine-rich protein 61 (CCN1/CYR61) are significantly shorter compared with those with low levels of CCN1. To identify the molecular mechanisms that regulate the expression of CCN1 in glioblastomas, we analyzed tumor samples from 42 patients with glioblastoma. Next-generation and Sanger sequencing techniques revealed that the PIK3R1Met326Ile mutation was significantly more frequent in patients with high vs low levels of CCN1 (9/22, 40.9% vs 2/20, 10.0%; respectively). Moreover, this mutation was identified in the corresponding blood samples. Univariate analysis of Kaplan-Meier survival data revealed that high levels of CCN1 and the presence of the PIK3R1Met326Ile mutation were significantly associated with PFS (p=0.0003 and 0.0191, respectively) and that age, high levels of CCN1, and the presence of the PIK3R1Met326Ile mutation were significantly associated with OS (p=0.0016, 0.0019 and 0.0057, respectively). Multivariate analysis identified age &gt;65 years and the presence of the PIK3R1Met326Ile mutation as prognostic factors for OS (HR=3.533 [1.519-8.220], p=0.003) and (HR=2.712 [1.187-6.198], p=0.018, respectively). We conclude that the germline mutation PIK3R1Met326Ile correlates with the levels of CCN1 and poor prognosis of glioblastoma.