The life history of 21 breast cancers.
Cell
; 149(5): 994-1007, 2012 May 25.
Article
em En
| MEDLINE
| ID: mdl-22608083
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Transformação Celular Neoplásica
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Evolução Clonal
/
Mutação
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido