바로가기  >

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.

Affiliations

Nalee Kim  1   2 , Se Hoon Kim  3   4 , Seok-Gu Kang  4   5 , Ju Hyung Moon  4   5 , Jaeho Cho  1   4 , Chang-Ok Suh  6 , Hong In Yoon  7   8 , Jong Hee Chang  9   10
1 Department of Radiation Oncology, Yonsei Cancer Center, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
2 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3 Department of Pathology, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
4 Brain Tumor Center, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
5 Department of Neurosurgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
6 Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Gyeonggi-Do, Republic of Korea.
7 Department of Radiation Oncology, Yonsei Cancer Center, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. yhi0225@yuhs.ac.
8 Brain Tumor Center, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. yhi0225@yuhs.ac.
9 Brain Tumor Center, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. changjh@yuhs.ac.
10 Department of Neurosurgery, Severance Hospital, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. changjh@yuhs.ac.