Canoy Reynand Jay, Shmakova Anna, Karpukhina Anna, Lomov Nikolai, Tiukacheva Eugenia, Kozhevnikova Yana, André Franck, Germini Diego, Vassetzky Yegor
UMR 9018, CNRS, Univ. Paris-Sud, Université Paris Saclay, Institut Gustave Roussy, F-94805 Villejuif, France.
Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, 1000 Manila, The Philippines.
NAR Cancer. 2023 Sep 23;5(3):zcad049. doi: 10.1093/narcan/zcad049. eCollection 2023 Sep.
Most cancer-related chromosomal translocations appear to be cell type specific. It is currently unknown why different chromosomal translocations occur in different cells. This can be due to either the occurrence of particular translocations in specific cell types or adaptive survival advantage conferred by translocations only in specific cells. We experimentally addressed this question by double-strand break (DSB) induction at , , and loci in the same cell to generate chromosomal translocations in different cell lineages. Our results show that any translocation can potentially arise in any cell type. We have analyzed different factors that could affect the frequency of the translocations, and only the spatial proximity between gene loci after the DSB induction correlated with the resulting translocation frequency, supporting the 'breakage-first' model. Furthermore, upon long-term culture of cells with the generated chromosomal translocations, only oncogenic - and - translocations persisted over a 60-day period. Overall, the results suggest that chromosomal translocation can be generated after DSB induction in any type of cell, but whether the cell with the translocation would persist in a cell population depends on the cell type-specific selective survival advantage that the chromosomal translocation confers to the cell.
大多数与癌症相关的染色体易位似乎具有细胞类型特异性。目前尚不清楚为何不同的染色体易位会发生在不同的细胞中。这可能是由于特定易位在特定细胞类型中的发生，或者是易位仅在特定细胞中赋予的适应性生存优势。我们通过在同一细胞的特定基因座处诱导双链断裂（DSB）来实验性地解决这个问题，以便在不同细胞谱系中产生染色体易位。我们的结果表明，任何易位都有可能在任何细胞类型中出现。我们分析了可能影响易位频率的不同因素，并且只有DSB诱导后基因座之间的空间接近度与产生的易位频率相关，这支持了“断裂优先”模型。此外，在对具有产生的染色体易位的细胞进行长期培养后，只有致癌性的特定易位在60天内持续存在。总体而言，结果表明在任何类型的细胞中DSB诱导后都可产生染色体易位，但具有易位的细胞是否会在细胞群体中持续存在取决于染色体易位赋予细胞的细胞类型特异性选择性生存优势。
