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Cell. 2012 May 25;149(5):994-1007. doi: 10.1016/j.cell.2012.04.023. Epub 2012 May 17.

The life history of 21 breast cancers.

Author information

  • 1Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

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PMID:
22608083
[PubMed - indexed for MEDLINE]
PMCID:
PMC3428864
Free PMC Article

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