The Life History of 21 Breast Cancers

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• 作者：Serena Nik-Zainal¹ ; ¹⁹ ; Peter Van  ; Loo¹ ; ² ; ³ ; ¹⁹ ; David  ; C. Wedge¹ ; ¹⁹ ; Ludmil  ; B. Alexandrov¹ ; Christopher  ; D. Greenman¹ ; ⁴ ; ⁵ ; King  ; Wai Lau¹ ; Keiran Raine¹ ; David Jones¹ ; John Marshall¹ ; Manasa Ramakrishna¹ ; Adam Shlien¹ ; Susanna  ; L. Cooke¹ ; Jonathan Hinton¹ ; Andrew Menzies¹ ; Lucy  ; A. Stebbings¹ ; Catherine Leroy¹ ; Mingming Jia¹ ; Richard Rance¹ ; Laura  ; J. Mudie¹ ; Stephen  ; J. Gamble¹ ; Philip  ; J. Stephens¹ ; Stuart McLaren¹ ; Patrick  ; S. Tarpey¹ ; Elli Papaemmanuil¹ ; Helen  ; R. Davies¹ ; Ignacio Varela¹ ; David  ; J. McBride¹ ; Graham  ; R. Bignell¹ ; Kenric Leung¹ ; Adam  ; P. Butler¹ ; Jon  ; W. Teague¹ ; Sancha Martin¹ ; Goran Jö ; nsson⁶ ; Odette Mariani⁷ ; Sandrine Boyault⁸ ; Penelope Miron⁹ ; Aquila Fatima⁹ ; Anita Langerø ; d¹⁰ ; Samuel  ; A.J.R. Aparicio¹¹ ; ¹² ; Andrew Tutt⁶ ; Anieta  ; M. Sieuwerts¹³ ; Å ; ke Borg¹⁴ ; Gilles Thomas⁸ ; Anne  ; Vincent Salomon⁷ ; Andrea  ; L. Richardson⁹ ; ¹⁵ ; Anne-Lise Bø ; rresen-Dale¹⁰ ; ¹⁶ ; P.  ; Andrew Futreal¹ ; Michael  ; R. Stratton¹ ; Peter  ; J. Campbell¹ ; ¹⁷ ; ¹⁸ ; ^{pc8@sanger.ac.uk} ; Breast Cancer Working Group of the International Cancer Genome Consortium
• 刊名：Cell
• 出版年：2012
• 期刊代码：50_00928674
• 类别：med
• 出版时间：25 May, 2012
• 卷：149
• 期：5
• 页码：994-1007
• 文件大小：2051 K

摘要

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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.

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