Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

被引：1586

作者：

Ding, Li ^{[1
,2
]}

Ley, Timothy J. ^{[1
,3
,4
]}

Larson, David E. ^{[1
]}

Miller, Christopher A. ^{[1
]}

Koboldt, Daniel C. ^{[1
]}

Welch, John S. ^{[3
]}

Ritchey, Julie K. ^{[3
]}

Young, Margaret A. ^{[3
]}

Lamprecht, Tamara ^{[3
]}

McLellan, Michael D. ^{[1
]}

McMichael, Joshua F. ^{[1
]}

Wallis, John W. ^{[1
,2
]}

Lu, Charles ^{[1
]}

Shen, Dong ^{[1
]}

Harris, Christopher C. ^{[1
]}

Dooling, David J. ^{[1
,2
]}

Fulton, Robert S. ^{[1
,2
]}

Fulton, Lucinda L. ^{[1
,2
]}

Chen, Ken ^{[1
,2
]}

Schmidt, Heather ^{[1
]}

Kalicki-Veizer, Joelle ^{[1
]}

Magrini, Vincent J. ^{[1
,2
]}

Cook, Lisa ^{[1
]}

McGrath, Sean D. ^{[1
]}

Vickery, Tammi L. ^{[1
]}

Wendl, Michael C. ^{[1
,2
]}

Heath, Sharon ^{[3
]}

Watson, Mark A. ^{[5
]}

Link, Daniel C. ^{[3
,4
]}

Tomasson, Michael H. ^{[3
,4
]}

Shannon, William D. ^{[6
]}

Payton, Jacqueline E. ^{[5
]}

Kulkarni, Shashikant ^{[2
,4
,5
]}

Westervelt, Peter ^{[3
,4
]}

Walter, Matthew J. ^{[3
,4
]}

Graubert, Timothy A. ^{[3
,4
]}

Mardis, Elaine R. ^{[1
,2
,4
]}

Wilson, Richard K. ^{[1
,2
,4
]}

DiPersio, John F. ^{[3
,4
]}

机构：

[1] Washington Univ, Genome Inst, St Louis, MO 63108 USA

[2] Washington Univ, Dept Genet, St Louis, MO 63110 USA

[3] Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA

[4] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA

[5] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA

[6] Washington Univ, Div Biostat, St Louis, MO 63110 USA

来源：

NATURE | 2012年 / 481卷 / 7382期

关键词：

ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; LYMPHOBLASTIC-LEUKEMIA; MISMATCHED HLA; MUTATIONS; METASTASIS; RESOLUTION; CANCER;

D O I：

10.1038/nature10738

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level(1,2). To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.

引用

页码：506 / 510

页数：5

共 28 条

[1] Genetic variegation of clonal architecture and propagating cells in leukaemia [J].

Anderson, Kristina ;

Lutz, Christoph ;

van Delft, Frederik W. ;

Bateman, Caroline M. ;

Guo, Yanping ;

Colman, Susan M. ;

Kempski, Helena ;

Moorman, Anthony V. ;

Titley, Ian ;

Swansbury, John ;

Kearney, Lyndal ;

Enver, Tariq ;

Greaves, Mel .

NATURE, 2011, 469 (7330) :356-+

[2]

Chen K, 2009, NAT METHODS, V6, P677, DOI [10.1038/NMETH.1363, 10.1038/nmeth.1363]

[3] Somatic mutations affect key pathways in lung adenocarcinoma [J].

Ding, Li ;

Getz, Gad ;

Wheeler, David A. ;

Mardis, Elaine R. ;

McLellan, Michael D. ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Greulich, Heidi ;

Muzny, Donna M. ;

Morgan, Margaret B. ;

Fulton, Lucinda ;

Fulton, Robert S. ;

Zhang, Qunyuan ;

Wendl, Michael C. ;

Lawrence, Michael S. ;

Larson, David E. ;

Chen, Ken ;

Dooling, David J. ;

Sabo, Aniko ;

Hawes, Alicia C. ;

Shen, Hua ;

Jhangiani, Shalini N. ;

Lewis, Lora R. ;

Hall, Otis ;

Zhu, Yiming ;

Mathew, Tittu ;

Ren, Yanru ;

Yao, Jiqiang ;

Scherer, Steven E. ;

Clerc, Kerstin ;

Metcalf, Ginger A. ;

Ng, Brian ;

Milosavljevic, Aleksandar ;

Gonzalez-Garay, Manuel L. ;

Osborne, John R. ;

Meyer, Rick ;

Shi, Xiaoqi ;

Tang, Yuzhu ;

Koboldt, Daniel C. ;

Lin, Ling ;

Abbott, Rachel ;

Miner, Tracie L. ;

Pohl, Craig ;

Fewell, Ginger ;

Haipek, Carrie ;

Schmidt, Heather ;

Dunford-Shore, Brian H. ;

Kraja, Aldi ;

Crosby, Seth D. ;

Sawyer, Christopher S. .

NATURE, 2008, 455 (7216) :1069-1075

[4] Genome remodelling in a basal-like breast cancer metastasis and xenograft [J].

Ding, Li ;

Ellis, Matthew J. ;

Li, Shunqiang ;

Larson, David E. ;

Chen, Ken ;

Wallis, Johnw. ;

Harris, Christopher C. ;

McLellan, Michael D. ;

Fulton, Robert S. ;

Fulton, Lucinda L. ;

Abbott, Rachel M. ;

Hoog, Jeremy ;

Dooling, David J. ;

Koboldt, Daniel C. ;

Schmidt, Heather ;

Kalicki, Joelle ;

Zhang, Qunyuan ;

Chen, Lei ;

Lin, Ling ;

Wendl, Michael C. ;

McMichael, Joshua F. ;

Magrini, Vincent J. ;

Cook, Lisa ;

McGrath, Sean D. ;

Vickery, Tammi L. ;

Appelbaum, Elizabeth ;

DeSchryver, Katherine ;

Davies, Sherri ;

Guintoli, Therese ;

Lin, Li ;

Crowder, Robert ;

Tao, Yu ;

Snider, Jacqueline E. ;

Smith, Scott M. ;

Dukes, Adam F. ;

Sanderson, Gabriel E. ;

Pohl, Craig S. ;

Delehaunty, Kim D. ;

Fronick, Catrina C. ;

Pape, Kimberley A. ;

Reed, Jerry S. ;

Robinson, Jody S. ;

Hodges, Jennifer S. ;

Schierding, William ;

Dees, Nathan D. ;

Shen, Dong ;

Locke, Devin P. ;

Wiechert, Madeline E. ;

Eldred, James M. ;

Peck, Josh B. .

NATURE, 2010, 464 (7291) :999-1005

[5] Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. [J].

Falini, B ;

Mecucci, C ;

Tiacci, E ;

Alcalay, M ;

Rosati, R ;

Pasqualucci, L ;

La Starza, R ;

Diverio, D ;

Colombo, E ;

Santucci, A ;

Bigerna, B ;

Pacini, R ;

Pucciarini, A ;

Liso, A ;

Vignetti, M ;

Fazi, P ;

Meani, N ;

Pettirossi, V ;

Saglio, G ;

Mandelli, F ;

Lo-Coco, F ;

Pelicci, P ;

Martelli, MF .

NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (03) :254-266

[6] ISOLATION OF A YEAST ARTIFICIAL CHROMOSOME SPANNING THE 8-21 TRANSLOCATION BREAKPOINT T(8-21)(Q22-Q22.3) IN ACUTE MYELOGENOUS LEUKEMIA [J].

GAO, JZ ;

ERICKSON, P ;

GARDINER, K ;

LEBEAU, MM ;

DIAZ, MO ;

PATTERSON, D ;

ROWLEY, JD ;

DRABKIN, HA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :4882-4886

[7] CYTOGENETIC STUDIES OF 103 PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA IN RELAPSE [J].

GARSON, OM ;

HAGEMEIJER, A ;

SAKURAI, M ;

REEVES, BR ;

SWANSBURY, GJ ;

WILLIAMS, GJ ;

ALIMENA, G ;

ARTHUR, DC ;

BERGER, R ;

DELACHAPELLE, A ;

DEWALD, GW ;

MITELMAN, F ;

VANDENBERGHE, H ;

LAWLER, SD ;

ROWLEY, JD .

CANCER GENETICS AND CYTOGENETICS, 1989, 40 (02) :187-202

[8] Mutations in the Wilms' tumor gene WT1 in leukemias [J].

KingUnderwood, L ;

Renshaw, J ;

PritchardJones, K .

BLOOD, 1996, 87 (06) :2171-2179

[9] A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignancies [J].

Kirito, Keita ;

Sakoe, Kumi ;

Shinoda, Daisuke ;

Takiyama, Yoshihisa ;

Kaushansky, Kenneth ;

Komatsu, Norio .

HAEMATOLOGICA, 2007, 93 (01) :155-156

[10] VarScan: variant detection in massively parallel sequencing of individual and pooled samples [J].

Koboldt, Daniel C. ;

Chen, Ken ;

Wylie, Todd ;

Larson, David E. ;

McLellan, Michael D. ;

Mardis, Elaine R. ;

Weinstock, George M. ;

Wilson, Richard K. ;

Ding, Li .

BIOINFORMATICS, 2009, 25 (17) :2283-2285

← 1 2 3 →