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Structural variant evolution after telomere crisis
DOI:10.1038/s41467-021-21933-7.png)
摘要
En 中文
Telomere crisis contributes to cancer genome evolution, yet only a subset of cancers display breakage-fusion-bridge (BFB) cycles and chromothripsis, hallmarks of experimental telomere crisis identified in previous studies. We examine the spectrum of structural variants (SVs) instigated by natural telomere crisis. Eight spontaneous post-crisis clones did not show prominent patterns of BFB cycles or chromothripsis. Their crisis-induced genome rearrangements varied from infrequent simple SVs to more frequent and complex SVs. In contrast, BFB cycles and chromothripsis occurred in MRC5 fibroblast clones that escaped telomere crisis after CRISPR-controlled telomerase activation. This system revealed convergent evolutionary lineages altering one allele of chromosome 12p, where a short telomere likely predisposed to fusion. Remarkably, the 12p chromothripsis and BFB events were stabilized by independent fusions to chromosome 21. The data establish that telomere crisis can generate a wide spectrum of SVs implying that a lack of BFB patterns and chromothripsis in cancer genomes does not indicate absence of past telomere crisis. Telomere crisis has been shown to induce chromothripsis and breakage fusion bridge (BFB) cycles in vitro. Here, the authors show that telomere crisis generates a much broader spectrum of structural variations, implying that cancers without chromothripsis and BFB cycles could have emerged from telomere crisis.
Keyword:
HUMAN-CELLS
MUTATIONAL PROCESSES
DNA-DAMAGE
REARRANGEMENT
IMMORTALIZATION
TRANSLOCATIONS
CHROMOTHRIPSIS
SENESCENCE
SIGNATURES
DELETION
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期刊
IF:
15.7
论文数:
9.3W
被引数:
91.2W
机构
引用论文
Chromosomal Translocations in Human Cells Are Generated by Canonical Nonhomologous End-Joining人类细胞中的染色体易位是通过规范的非同源末端连接产生的
MOLECULAR CELL
IF16.6

