Portal de Periódicos da CAPES

The Life History of 21 Breast Cancers

2012; Cell Press; Volume: 149; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2012.04.023

1097-4172

Serena Nik‐Zainal, Peter Van Loo, David C. Wedge, Ludmil B. Alexandrov, Christopher Greenman, King Wai Lau, Keiran Raine, David Jones, John Marshall, Manasa Ramakrishna, Adam Shlien, Susanna L. Cooke, Jonathan Hinton, Andrew Menzies, Lucy Stebbings, Catherine Leroy, Mingming Jia, Richard Rance, Laura Mudie, Stephen J. Gamble, Philip J. Stephens, Stuart McLaren, Patrick Tarpey, Elli Papaemmanuil, Helen Davies, Ignacio Varela, David J. McBride, Graham R. Bignell, Kenric Leung, Adam P. Butler, Jon W. Teague, Sancha Martin, Göran Jönsson, Odette Mariani, Sandrine Boyault, Penelope Miron, Aquila Fatima, Anita Langerød, Samuel Aparício, Andrew Tutt, Anieta M. Sieuwerts, Åke Borg, Anthony J. Gill, Anne Vincent‐Salomon, Andrea L. Richardson, Anne‐Lise Børresen‐Dale, P. Andrew Futreal, Michael R. Stratton, Peter J. Campbell,

Single-cell and spatial transcriptomics

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.