Title: The life history of 21 breast cancers
Authors: 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 ×
Breast Cancer Working Group of the International Cancer Genome Consortium #
Issue Date: May-2012
Publisher: MIT Press
Series Title: Cell vol:149 issue:5 pages:994-1007
Article number: 10.1016/j.cell.2012.04.023
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.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Human Genome Laboratory
* (joint) first author
× corresponding author
# (joint) last author

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