ATM mutations improve radio-sensitivity in wild-type isocitrate dehydrogenase-associated high-grade glioma: retrospective analysis using next-generation sequencing data

摘要

To identify the association between somatic ataxia-telangiectasia mutated (ATM) mutations and improved radio-sensitivity, we retrospectively reviewed next-generation sequencing data from patients diagnosed with isocitrate dehydrogenase (IDH)-wildtype high-grade glioma. We included 39 individuals with (IDH)-wildtype high-grade glioma (diffuse astrocytoma n?=?2, anaplastic astrocytoma n?=?10, and glioblastoma n?=?27) not subjected to gross tumor resection and undergoing radiation therapy with a median total dose of 60?Gy in 30 fractions. The mutational status of the ATM gene was obtained through next-generation sequencing using a TruSight Tumor 170 cancer panel. Disease progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria as well as neurologic and clinical findings. Among the 39 samples, ATM mutations (ATM mut( )) were detected in 26% of cases (n?=?10). No significant differences were observed in the characteristics of the patients or tumors. Among the 10 patients in the ATM mut( ) group, there were 6 patients with glioblastoma and 4 patients with anaplastic astrocytoma. Most mutations were missense mutations (n?=?8, 80%). With a median follow-up of 16.5 mo (interquartile range, 11.4–19.8), ATM mut( ) exhibited 1-year in-field control of 100% compared with 44.1% in the ATM mut(?) group (p?=?0.002). There was no difference in the out-field control rate or overall survival between the two groups (p?=?0.861 and p?=?0.247, respectively). Our results demonstrated that ATM mutations might be involved in the increased radio-sensitivity with excellent in-field control despite the aggressive nature of IDH-wildtype high-grade glioma. Further studies are necessary to uncover the potential role of ATM as a biomarker and candidate therapeutic target in high-grade gliomas.