Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

Autor:	Youk J; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea., Kwon HW; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Republic of Korea., Lim J; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Genome Insight, Inc., San Diego, CA 92121, USA., Kim E; Department of Radiation Oncology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, 20, Boramae-ro 5 Gil, Dongjak-gu, Seoul 07061, Republic of Korea; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea., Kim T; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea., Kim R; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Genome Insight, Inc., San Diego, CA 92121, USA., Park S; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Genome Insight, Inc., San Diego, CA 92121, USA., Yi K; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Genome Insight, Inc., San Diego, CA 92121, USA., Nam CH; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea., Jeon S; Department of Biological Sciences & IMBG, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea., An Y; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea., Choi J; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, CB2 0AW Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3EL Cambridge, UK., Na H; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria., Lee ES; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Cho Y; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea., Min DW; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea., Kim H; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Kang YR; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Choi SH; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Bae MJ; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Lee CG; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Kim JG; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; KI for Health Science and Technology, KAIST, Daejeon 34141, Republic of Korea., Kim YS; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; KI for Health Science and Technology, KAIST, Daejeon 34141, Republic of Korea., Yu T; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Science, Busan 46033, Republic of Korea., Lee WC; Genome Insight, Inc., San Diego, CA 92121, USA., Shin JY; Genome Insight, Inc., San Diego, CA 92121, USA., Lee DS; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea., Kim TY; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; Cancer Research Institute, Seoul National University, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea., Ku T; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; KI for Health Science and Technology, KAIST, Daejeon 34141, Republic of Korea., Kim SY; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea., Lee JH; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, CB2 0AW Cambridge, UK; Department of Physiology, Development and Neuroscience, University of Cambridge, CB2 3EL Cambridge, UK., Koo BK; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria., Lee H; Department of Biological Sciences & IMBG, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea., Yi OV; Department of Breast Surgery, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Han EC; Department of Surgery, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea., Chang JH; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jh.chang@snu.ac.kr., Kim KS; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: kskim.cirt@snu.ac.kr., Son TG; Research Center, Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea. Electronic address: tgson@dirams.re.kr., Ju YS; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; Genome Insight, Inc., San Diego, CA 92121, USA. Electronic address: ysju@kaist.ac.kr.
Jazyk:	angličtina
Zdroj:	Cell genomics [Cell Genom] 2024 Feb 14; Vol. 4 (2), pp. 100499.
DOI:	10.1016/j.xgen.2024.100499
Abstrakt:	The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes. Competing Interests: Declaration of interests Y.S.J. is a genomic co-founder and chairman of Genome Insight. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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