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  • [Int J Radiat Biol.] Targeted next-generation DNA sequencing identifies Notch signaling pathway mutation as a predictor of radiation response.

    [Int J Radiat Biol.] Targeted next-generation DNA sequencing identifies Notch signaling pathway mutation as a predictor of radiation response.

    서울의대 / 전승혁, 지의규*

  • 출처
    Int J Radiat Biol.
  • 등재일
    2019 Sep 26:1-8. doi: 10.1080/09553002.2019.166521
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    Abstract
    Purpose: Identifying the association between somatic mutations and the radiation response of tumor is essential for understanding the mechanisms and practicing personalized radiotherapy. The present study aimed to discover specific genes or pathways that are associated with radiation response using targeted next-generation DNA sequencing. Material and methods: Fifty-five patients with various solid tumors whose specimen were sequenced using institutional panel which includes 148 cancer-related genes and received radiotherapy for a measurable tumor were analyzed. Patients with irradiated tumors in complete or partial remission for more than 6 months were defined as responders. Association between mutations including pathogenic single nucleotide variants and insertions/deletions in the 148 genes and 39 molecular pathways and radiation response was investigated. Results: Analyzing 17 responders and 38 non-responders, biologically effective dose (BED), but not concurrent chemotherapy, was associated with radiation response. No single gene correlated with radiation response. Mutations in Notch signaling pathway were associated with radiosensitivity after correction for multiple comparison (adjusted p = .094). When BED and Notch signaling pathway mutation were tested with logistic regression, both variables were associated with radiation response. Conclusions: Our results suggest that somatic mutations in Notch signaling pathway may be related to sensitivity to radiation, although these results should be validated in a larger and more homogeneous cohort.

     


    Author information

    Jeon SH1, Chie EK1,2, Kim YJ1, Lee KH3, Lee HS4, Kim MJ5, Im SA3, Kim JI6, Kim TY3,5.
    1
    Department of Radiation Oncology, Seoul National University College of Medicine , Seoul , Korea.
    2
    Institute of Radiation Medicine, Seoul National University Medical Research Center , Seoul , Korea.
    3
    Department of Internal Medicine, Seoul National University College of Medicine , Seoul , Korea.
    4
    Biomedical Research Institute, Seoul National University Hospital , Seoul , Korea.
    5
    Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University , Seoul , Korea.
    6
    Department of Biomedical Sciences, Seoul National University College of Medicine , Seoul , Korea.

  • 키워드
    Radiotherapy; molecular pathway; next-generation sequencing; radiogenomics; radiosensitivity; targeted sequencing
  • 연구소개
    종양에서의 유전 변이 발현에 따른 방사선 치료 반응의 차이를 보고자 한 논문입니다. 다양한 암종으로 유전체 분석을 시행하였던 환자 중 방사선 치료를 받았던 55명의 환자를 대상으로 148개의 유전체와 39개의 분자경로와 방사선 치료 반응을 분석하였습니다. 방사선량 이외에 특정 변이는 치료 반응과 연관성을 확인하지 못하였으나, Notch 신호 체계의 변이와 치료 반응과의 연관성을 확인할 수 있었습니다. 추후 균일한 더 많은 환자를 대상으로 분석하여, 유전체 기반 치료 반응을 예측 연구에 도움이 될 수 있겠습니다.
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