期刊
CELL
卷 149, 期 5, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.cell.2012.04.023
关键词
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资金
- Wellcome Trust [098051]
- Breakthrough Breast Cancer Research [ICGC 08/09]
- National Research Council Canada
- EMBO
- International Human Frontier Science Program Organization
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO)
- Norwegian Research Council
- Norwegian Cancer Society
- Radium Hospital Foundation
- Health Region South-East
- European Community [242006]
- National Cancer Institute Specialized Program Of Research Excellence [CA089393]
- Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre
- St Thomas' NHS Foundation Trust
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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