Structural variant evolution after telomere crisis

Abstract Telomere crisis contributes to cancer genome evolution, yet only a subset of cancers display breakage-fusion-bridge (BFB) cycles and chromothripsis, hallmarks experimental telomere identified in previous studies. We examine the spectrum structural variants (SVs) instigated by natural crisis. Eight spontaneous post-crisis clones did not show prominent patterns BFB or chromothripsis. Their crisis-induced rearrangements varied from infrequent simple SVs more frequent complex SVs. In contrast, chromothripsis occurred MRC5 fibroblast that escaped after CRISPR-controlled telomerase activation. This system revealed convergent evolutionary lineages altering one allele chromosome 12p, where short likely predisposed fusion. Remarkably, 12p events were stabilized independent fusions 21. The data establish can generate wide implying lack genomes does indicate absence past