Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.

ABSTRACT: Both the presence of an abnormal complement of chromosomes (aneuploidy) and an increased frequency of chromosome missegregation (chromosomal instability) are hallmarks of cancer. Analyses of cancer genome data have identified certain aneuploidy patterns in tumors; however, the bases behind their selection are largely unexplored. By establishing time-resolved long-term adaptation protocols, we found that human cells adapt to persistent spindle assembly checkpoint (SAC) inhibition by acquiring specific chromosome arm gains and losses. Independently adapted populations converge on complex karyotypes, which over time are refined to contain ever smaller chromosomal changes. Of note, the frequencies of chromosome arm gains in adapted cells correlate with those detected in cancers, suggesting tha

SUBMITTER: Adell MAY 

PROVIDER: S-EPMC10111865 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature