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Increased Radiosensitivity of Solid Tumors Harboring ATM and BRCA1/2 Mutations

 Kyung Hwan Kim  ;  Han Sang Kim  ;  Seung-Seob Kim  ;  Hyo Sup Shim  ;  Andrew Jihoon Yang  ;  Jason Joon Bock Lee  ;  Hong In Yoon  ;  Joong Bae Ahn  ;  Jee Suk Chang 
 CANCER RESEARCH AND TREATMENT, Vol.54(1) : 54-64, 2022-01 
Journal Title
Issue Date
ATM ; BRCA ; DNA repair ; Radiosensitivity ; Radiotherapy
Purpose: Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT.

Materials and methods: Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2.

Results: Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680).

Conclusion: Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 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
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Hwan(김경환)
Kim, Seung-seob(김승섭) ORCID logo https://orcid.org/0000-0001-6071-306X
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Yang, Andrew Jihoon(양지훈) ORCID logo https://orcid.org/0000-0002-1635-4036
Yoon, Hong In(윤홍인) ORCID logo https://orcid.org/0000-0002-2106-6856
Lee, Jason Joon Bock(이준복)
Chang, Jee Suk(장지석) ORCID logo https://orcid.org/0000-0001-7685-3382
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