Radiation Oncology (Jul 2020)

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

  • Nalee Kim,
  • Se Hoon Kim,
  • Seok-Gu Kang,
  • Ju Hyung Moon,
  • Jaeho Cho,
  • Chang-Ok Suh,
  • Hong In Yoon,
  • Jong Hee Chang

DOI
https://doi.org/10.1186/s13014-020-01619-y
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 11

Abstract

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Abstract Background 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. Methods 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. Results 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). Conclusions 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.

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