Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution.

ABSTRACT:

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The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event i

SUBMITTER: Dewhurst SM 

PROVIDER: S-EPMC4293454 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature