Genomic Evolution of Breast Cancer Metastasis and Relapse

被引：489

作者：

Yates, Lucy R. ^{[1
,2
]}

Knappskog, Stian ^{[3
,4
]}

Wedge, David ^{[1
,5
]}

Farmery, James H. R. ^{[6
]}

Gonzalez, Santiago ^{[1
,7
]}

Martincorena, Inigo ^{[1
]}

Alexandrov, Ludmil B. ^{[8
,9
,10
]}

Van Loo, Peter ^{[11
,12
]}

Haugland, Hans Kristian ^{[13
,14
]}

Lilleng, Peer Kaare ^{[13
,14
]}

Gundem, Gunes ^{[1
,15
]}

Gerstung, Moritz ^{[1
,7
]}

Pappaemmanuil, Elli ^{[1
,15
]}

Gazinska, Patrycja ^{[16
]}

Bhosle, Shriram G. ^{[1
]}

Jones, David ^{[1
]}

Raine, Keiran ^{[1
]}

Mudie, Laura ^{[1
]}

Latimer, Calli ^{[1
]}

Sawyer, Elinor ^{[2
,16
]}

Desmedt, Christine ^{[17
]}

Sotiriou, Christos ^{[17
]}

Stratton, Michael R. ^{[1
]}

Sieuwerts, Anieta M. ^{[18
]}

Lynch, Andy G. ^{[6
]}

Martens, John W. ^{[18
]}

Richardson, Andrea L. ^{[19
,20
]}

Tutt, Andrew ^{[16
,21
,22
]}

Lonning, Per Eystein ^{[3
,4
]}

Campbell, Peter J. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England

[2] Guys & St Thomas NHS Trust, Dept Clin Oncol, London SE1 9RT, England

[3] Univ Bergen, Sect Oncol, Dept Clin Sci, Bergen, Norway

[4] Haukeland Hosp, Dept Oncol, Bergen, Norway

[5] Univ Oxford, Big Data Inst, Oxford OX3 7BN, England

[6] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England

[7] European Bioinformat Inst EMBL EBI, Wellcome Genome Campus, Hinxton CB10 1SD, England

[8] Los Alamos Natl Lab, Theoret Biol & Biophys T 6, Los Alamos, NM 87545 USA

[9] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA

[10] Univ New Mexico, Ctr Comprehens Canc, Albuquerque, NM 87102 USA

[11] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England

[12] Univ Leuven, Dept Human Genet, B-3000 Leuven, Belgium

[13] Haukeland Hosp, Dept Pathol, Bergen, Norway

[14] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway

[15] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, Computat Oncol, New York, NY 10065 USA

[16] Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London SE1 9RT, England

[17] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab, Bd Waterloo 121, B-1000 Brussels, Belgium

[18] Erasmus Univ, Med Ctr, Erasmus MC Canc Inst & Canc Genom Netherlands, Dept Med Oncol, Rotterdam, Netherlands

[19] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[20] Dana Farber Canc Inst, Boston, MA 02215 USA

[21] Kings Coll London, Breast Canc Now Res Unit, London SE1 9RT, England

[22] Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London SW3 6JB, England

来源：

CANCER CELL | 2017年 / 32卷 / 02期

基金：

美国能源部; 英国惠康基金; 英国医学研究理事会;

关键词：

TUMOR GENETIC-HETEROGENEITY; MUTATIONAL PROCESSES; AROMATASE INHIBITION; THERAPEUTIC TARGETS; SOMATIC MUTATIONS; ESR1; MUTATIONS; LANDSCAPE; RESISTANCE; AMPLIFICATION; PROGRESSION;

D O I：

10.1016/j.ccell.2017.07.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

引用

页码：169 / +

页数：23

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