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

Authors
 Nalee Kim  ;  Se Hoon Kim  ;  Seok-Gu Kang  ;  Ju Hyung Moon  ;  Jaeho Cho  ;  Chang-Ok Suh  ;  Hong In Yoon  ;  Jong Hee Chang 
Citation
 RADIATION ONCOLOGY, Vol.15(1) : 184, 2020-07 
Journal Title
 RADIATION ONCOLOGY 
Issue Date
2020-07
Keywords
ATM ; IDH-wild type high-grade glioma ; Next-generation sequencing ; Radiation therapy ; Radiosensitivity
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.
Files in This Item:
T202003050.pdf Download
DOI
10.1186/s13014-020-01619-y
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Nalee(김나리) ORCID logo https://orcid.org/0000-0003-4742-2772
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Moon, Ju Hyung(문주형)
Suh, Chang Ok(서창옥)
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Chang, Jong Hee(장종희) ORCID logo https://orcid.org/0000-0003-1509-9800
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179493
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