Journal article
Tolerance of whole- genome doubling propagates chromosomal instability and accelerates cancer genome evolution
SM Dewhurst, N McGranahan, RA Burrell, AJ Rowan, E Grönroos, D Endesfelder, T Joshi, D Mouradov, P Gibbs, RL Ward, NJ Hawkins, Z Szallasi, OM Sieber, C Swanton
Cancer Discovery | Published : 2014
Abstract
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 cha..
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Awarded by Medical Research Council
Funding Acknowledgements
This project was funded by grants from CRUK (to S. M. Dewhurst, N. McGranahan, R. A. Burrell, and C. Swanton), the Medical Research Council (to A.J. Rowan and C. Swanton; ID: G0701935/2), EU Framework 7 (to E. Gronroos, C. Swanton, T. Joshi, and Z. Szallasi; projects PREDICT and RESPONSIFY), The Prostate Cancer Foundation (to C. Swanton), The Rosetree Trust (to C. Swanton), The Breast Cancer Foundation (to C. Swanton), and the NHMRC through a Project Grant (Application ID 489418; to O.M. Sieber, P. Gibbs, and R. L. Ward), and supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre.