The Life History of 21 Breast Cancers
Abstrak
Summary 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. PaperClip
Penulis (49)
S. Nik-Zainal
Peter Van Loo
D. Wedge
Ludmil B. Alexandrov
Christopher D. Greenman
K. Lau
K. Raine
David Jones
J. Marshall
Manasa Ramakrishna
A. Shlien
S. Cooke
Jonathan Hinton
A. Menzies
L. Stebbings
Catherine Leroy
Mingming Jia
Richard Rance
L. Mudie
Stephen J. Gamble
Philip J. Stephens
Stuart McLaren
P. Tarpey
E. Papaemmanuil
Helen R. Davies
I. Varela
D. Mcbride
G. Bignell
Kenric Leung
Adam P. Butler
J. Teague
Sancha Martin
G. Jönsson
O. Mariani
S. Boyault
P. Miron
Aquila Fatima
A. Langerød
Samuel Aparicio
A. Tutt
A. Sieuwerts
Å. Borg
G. Thomas
A. Salomon
Andrea L. Richardson
A. Børresen-Dale
P. Futreal
Michael R. Stratton
P. Campbell
Akses Cepat
- Tahun Terbit
- 2012
- Bahasa
- en
- Total Sitasi
- 1448×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1016/j.cell.2012.04.023
- Akses
- Open Access ✓