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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

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

Erratum in

  • Cell. 2015 Aug 13;162(4):924.

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.

PMID:
22608083
PMCID:
PMC3428864
DOI:
10.1016/j.cell.2012.04.023
[Indexed for MEDLINE]
Free PMC Article

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