The Life History of 21 Breast Cancers

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.

DOI: 10.1016/j.cell.2015.07.039

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@inproceedings{NikZainal2012TheLH, title={The Life History of 21 Breast Cancers}, author={Serena Nik-Zainal and Peter Van Loo and D. Eugene Wedge and Ludmil B. Alexandrov and Christopher D. Greenman and King Wai Lau and Keiran Raine and David Jones and John C. Marshall and Manasa Ramakrishna and Adam Shlien and Susanna L. Cooke and Jonathan W. Hinton and Andrew Menzies and Lucy A. Stebbings and Catherine Leroy and Mingming Jia and Richard Rance and Laura J. Mudie and Stephen J. Gamble and Philip J. Stephens and Stuart J. McLaren and Patrick S. Tarpey and Elli Papaemmanuil and Helen R. Davies and Ignacio Varela and David J. McBride and Graham R. Bignell and Kenric Leung and Adam P. Butler and Jon W. Teague and Sancha Martin and Goran J{\"{o}nsson and Odette Mariani and Sandrine Boyault and Penelope L. Miron and Aquila Fatima and Anita Langer\od and Samuel A.J.R. Aparicio and Andrew N Tutt and Anieta M. Sieuwerts and {\AA}ke Borg and Gilles D. Thomas and Anne Vincent Salomon and Andrea L. Richardson and Anne-Lise B\orresen-Dale and P. Andy Futreal and Michael R. Stratton and Peter J. Campbell}, booktitle={Cell}, year={2012} }