[HTML][HTML] The life history of 21 breast cancers

S Nik-Zainal, P Van Loo, DC Wedge, LB Alexandrov… - Cell, 2012 - cell.com
S Nik-Zainal, P Van Loo, DC Wedge, LB Alexandrov, CD Greenman, KW Lau, K Raine…
Cell, 2012cell.com
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 …
Summary
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.
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