Quantitative and qualitative mutational impact of ionizing radiation on normal cellsopen access
- Authors
- Youk, Jeonghwan; Kwon, Hyun Woo; Lim, Joonoh; Kim, Eunji; Kim, Taewoo; Kim, Ryul; Park, Seongyeol; Yi, Kijong; Nam, Chang Hyun; Jeon, Sara; An, Yohan; Choi, Jinwook; Na, Hyelin; Lee, Eon-Seok; Cho, Youngwon; Min, Dong-Wook; Kim, Hyojin; Kang, Yeong-Rok; Choi, Si Ho; Bae, Min Ji; Lee, Chang Geun; Kim, Joon-Goon; Kim, Young Seo; Yu, Tosol; Lee, Won-Chul; Shin, Jong-Yeon; Lee, Dong Soo; Kim, Tae-You; Ku, Taeyun; Kim, Su Yeon; Lee, Joo-Hyeon; Koo, Bon-Kyoung; Lee, Hyunsook; Yi, On Vox; Han, Eon Chul; Chang, Ji Hyun; Kim, Kyung Su; Son, Tae Gen; Seok, Young
- Issue Date
- Feb-2024
- Publisher
- Elsevier
- Citation
- Cell Genomics, v.4, no.2
- Indexed
- SCOPUS
ESCI
- Journal Title
- Cell Genomics
- Volume
- 4
- Number
- 2
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/66005
- DOI
- 10.1016/j.xgen.2024.100499
- ISSN
- 2666-979X
- Abstract
- 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.
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