The life history of 21 breast cancers

Nik-Zainal, Serena, Van Loo, Peter, Wedge, David C., Alexandrov, Ludmil B., Greenman, Christopher D., Lau, King Wai, Raine, Keiran, Jones, David, Marshall, John, Ramakrishna, Manasa, Shlien, Adam, Cooke, Susanna L., Hinton, Jonathan, Menzies, Andrew, Stebbings, Lucy A., Leroy, Catherine, Jia, Mingming, Rance, Richard, Mudie, Laura J., Gamble, Stephen J., Stephens, Philip J., McLaren, Stuart, Tarpey, Patrick S., Papaemmanuil, Elli, Davies, Helen R., Varela, Ignacio, McBride, David J., Bignell, Graham R., Leung, Kenric, Butler, Adam P., Teague, Jon W., Martin, Sancha, Jönsson, Göran, Mariani, Odette, Boyault, Sandrine, Miron, Penelope, Fatima, Aquila, Langerød, Anita, Aparicio, Samuel A. J. R., Tutt, Andrew, Sieuwerts, Anieta M., Borg, Åke, Thomas, Gilles, Vincent Salomon, Anne, Richardson, Andrea L., Børresen-Dale, Anne-Lise, Futreal, P. Andrew, Stratton, Michael R. and Campbell, Peter J. (2012) The life history of 21 breast cancers. Cell, 149 (5). pp. 994-1007. ISSN 0092-8674

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Abstract

Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Computing Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Computational Biology
Depositing User:	Pure Connector
Date Deposited:	09 Jun 2014 20:46
Last Modified:	18 Apr 2023 11:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/48574
DOI:	10.1016/j.cell.2012.04.023

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