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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 and Ramakrishna, Manasa, et al. (2012) In Cell 149(5).
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
in
Cell
volume
149
issue
5
publisher
Cell Press
external identifiers
  • wos:000304453900007
  • scopus:84861550476
ISSN
1097-4172
DOI
10.1016/j.cell.2012.04.023
project
CREATE Health
language
English
LU publication?
yes
id
3a276696-71b1-405d-887f-b74233425358 (old id 2906918)
date added to LUP
2012-08-01 09:47:15
date last changed
2017-11-19 03:24:51
@article{3a276696-71b1-405d-887f-b74233425358,
  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.},
  author       = {Nik-Zainal, Serena and Van Loo, Peter and Wedge, David C. and Alexandrov, Ludmil B. and Greenman, Christopher D. and Lau, King Wai and Raine, Keiran and Jones, David and Marshall, John and Ramakrishna, Manasa and Shlien, Adam and Cooke, Susanna L. and Hinton, Jonathan and Menzies, Andrew and Stebbings, Lucy A. and Leroy, Catherine and Jia, Mingming and Rance, Richard and Mudie, Laura J. and Gamble, Stephen J. and Stephens, Philip J. and McLaren, Stuart and Tarpey, Patrick S. and Papaemmanuil, Elli and Davies, Helen R. and Varela, Ignacio and McBride, David J. and Bignell, Graham R. and Leung, Kenric and Butler, Adam P. and Teague, Jon W. and Martin, Sancha and Joensson, Goran and Mariani, Odette and Boyault, Sandrine and Miron, Penelope and Fatima, Aquila and Langerod, Anita and Aparicio, Samuel A. J. R. and Tutt, Andrew and Sieuwerts, Anieta M. and Borg, Åke and Thomas, Gilles and Salomon, Anne Vincent and Richardson, Andrea L. and Borresen-Dale, Anne-Lise and Futreal, P. Andrew and Stratton, Michael R. and Campbell, Peter J.},
  issn         = {1097-4172},
  language     = {eng},
  number       = {5},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {The Life History of 21 Breast Cancers},
  url          = {http://dx.doi.org/10.1016/j.cell.2012.04.023},
  volume       = {149},
  year         = {2012},
}