[Clinicopathological and molecular genetic characteristics of adult IDH wild-type diffuse gliomas]

Objective: To analyze the clinicopathological and molecular features and prognostic implications of adult isocitrate dehydrogenase wild type (IDH-wt) diffuse gliomas. Methods: A total of 87 cases of adult IDH-wt diffuse gliomas from 2016 to 2020 in Xuanwu Hospital of Capital Medical University were retrospectively collected. The clinicopathological characteristics and prognosis were analyzed. Molecular characteristics were also analyzed using Sanger sequencing and next generation sequencing. Results: There were 53 males and 34 females, aged from 19 to 78 years (mean 53 years). Histopathologically, there were 63 (72.4%) glioblastomas, 16 (18.4%) anaplastic astrocytomas, six (6.9%) diffuse astrocytomas, and one (1.1%) each of anaplastic oligodendrocytoma, and anaplastic oligodendroglioma. Common molecular genetic changes in IDH-wt gliomas included TERT promoter mutation which was found in 60 cases (69.0%); MGMT promoter methylation in 43 cases (49.4%); EGFR mutation in 38 cases (43.7%); PTEN mutation in 35 cases (40.2%) and TP53 mutation in 32 cases (36.8%). In addition, PDGFRA mutation was detected in 17 cases (19.5%), CDK4 amplification in 15 cases (17.2%) and MDM2 amplification in 11 cases (12.6%). In IDH-wt diffuse gliomas, there was no significant difference in the overall survival between TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4, MDM2 mutations and the wild-type, since these gene mutations could co-occur in any case (P>0.05). Also there was no significant difference in the overall survival between the WHO grade Ⅱ/Ⅲ gliomas and glioblastoma patients with these gene mutations (P>0.05). Conclusions: TERT promoter, EGFR, PTEN, TP53, PDGFRA, CDK4 and MDM2 gene mutations are common molecular genetic changes in adult IDH-wt gliomas, and are associated with poor prognosis. It is suggested that these genes are potentially useful for predicting the prognosis and should be tested in adult IDH-wt gliomas.