电离辐射致基因组突变的特征分析

Objective:To investigate the characteristics of genomic mutations induced by ionizing radiation in humaninduced pluripotent stem cells by sequencing technology-base mutaion detection approach.Methods:Cells were treated with 2 Gy and 4 Gy X-rays, with untreated controls and cisplatin-treated groups as comparisons. After treatment, singleclone cells were obtained via limiting dilution, and genomic DNA was extracted for whole-genome sequencing. A mutation detection and analysis workflow was established. The mutation spectra of single-base substitutions (SBS-96) and insertion/deletions (ID-83) were analyzed using the COSMIC database and SigProfiler tool. Transcriptional strand bias and mutation distribution patterns were evaluated, and chromosomal aberrations (deletions, duplications, inversions, and translocations) were analyzed to explore the effects of ionizing radiation on genomic mutations.Results: Ionizing radiation mainly induced 1 bp deletions, inversions, and translocations. After ionizing radiation treatment, the number of loss of heterozygosity increased, but the number of single nucleotide variants did notincrease.Conclusion:The genome mutations induced by ionizing radiation are primarily characterized by indels and large-scale structural variations, reflecting mutations generated during the repair of DNA double-strand breaks caused by ionizing radiation. There is no simple linear relationship between the mutation number and radiation dose.