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The life history of 21 breast cancers.

Nik-Zainal, Serena; Van Loo, Peter; Wedge, David C; Alexandrov, Ludmil B; Greenman, Christopher D; Lau, King Wai; Raine, Keiran; Jones, David; Marshall, John; Ramakrishna, Manasa; Shlien, Adam; Cooke, Susanna L; Hinton, Jonathan; Menzies, Andrew; Stebbings, Lucy A; Leroy, Catherine; Jia, Mingming; Rance, Richard; Mudie, Laura J; Gamble, Stephen J; Stephens, Philip J; McLaren, Stuart; Tarpey, Patrick S; Papaemmanuil, Elli; Davies, Helen R; Varela, Ignacio; McBride, David J; Bignell, Graham R; Leung, Kenric; Butler, Adam P; Teague, Jon W; Martin, Sancha; Jönsson, Goran; Mariani, Odette; Boyault, Sandrine; Miron, Penelope; Fatima, Aquila; Langerød, Anita; Aparicio, Samuel A J R; Tutt, Andrew; Sieuwerts, Anieta M; Borg, Åke; Thomas, Gilles; Salomon, Anne Vincent; Richardson, Andrea L; Børresen-Dale, Anne-Lise; Futreal, P Andrew; Stratton, Michael R; Campbell, Peter J.
Cell; 149(5): 994-1007, 2012 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-22608083
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.
Selo DaSilva