Divergent clonal selection dominates medulloblastoma at recurrence

被引：239

作者：

Morrissy, A. Sorana ^{[1
,2
]}

Garzia, Livia ^{[1
,2
]}

Shih, David J. H. ^{[1
,2
,3
]}

Zuyderduyn, Scott ^{[4
]}

Huang, Xi ^{[1
]}

Skowron, Patryk ^{[1
,2
,3
]}

Remke, Marc ^{[5
]}

Cavalli, Florence M. G. ^{[1
,2
]}

Ramaswamy, Vijay ^{[1
,2
,3
,6
]}

Lindsay, Patricia E. ^{[7
,8
]}

Jelveh, Salomeh ^{[8
]}

Donovan, Laura K. ^{[1
,2
]}

Wang, Xin ^{[1
,2
,3
]}

Luu, Betty ^{[1
,2
]}

Zayne, Kory ^{[1
,2
]}

Li, Yisu ^{[9
]}

Mayoh, Chelsea ^{[9
]}

Thiessen, Nina ^{[9
]}

Mercier, Eloi ^{[9
]}

Mungall, Karen L. ^{[9
]}

Ma, Yusanne ^{[9
]}

Tse, Kane ^{[9
]}

Zeng, Thomas ^{[9
]}

Shumansky, Karey ^{[10
]}

Roth, Andrew J. L. ^{[10
]}

Shah, Sohrab ^{[10
]}

Farooq, Hamza ^{[1
,2
]}

Kijima, Noriyuki ^{[1
,2
]}

Holgado, Borja L. ^{[1
,2
]}

Lee, John J. Y. ^{[1
,2
,3
]}

Matan-Lithwick, Stuart ^{[1
,2
]}

Liu, Jessica ^{[1
,2
]}

Mack, Stephen C. ^{[1
,2
,11
]}

Manno, Alex ^{[1
,2
]}

Michealraj, K. A. ^{[1
,2
]}

Nor, Carolina ^{[1
,2
]}

Peacock, John ^{[1
,2
,3
]}

Qin, Lei ^{[1
,2
]}

Reimand, Juri ^{[2
,4
]}

Rolider, Adi ^{[1
,2
]}

Thompson, Yuan Y. ^{[1
,2
,3
]}

Wu, Xiaochong ^{[1
,2
]}

Pugh, Trevor ^{[12
]}

Ally, Adrian ^{[9
]}

Bilenky, Mikhail ^{[9
]}

Butterfield, Yaron S. N. ^{[9
]}

Carlsen, Rebecca ^{[9
]}

Cheng, Young ^{[9
]}

Chuah, Eric ^{[9
]}

Corbett, Richard D. ^{[9
]}

机构：

[1] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 0A4, Canada

[2] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada

[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 0A4, Canada

[4] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada

[5] Univ Hosp Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol, Dusseldorf, Germany

[6] Hosp Sick Children, Div Neurosurg, Toronto, ON M5S 3E1, Canada

[7] Univ Toronto, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada

[8] Univ Hlth Network, Princess Margaret Canc Ctr, Radiat Med Program, Toronto, ON M5G 2M9, Canada

[9] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada

[10] BC Canc Agcy, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada

[11] Cleveland Clin Fdn, Ctr Stem Cell & Regenerat Med, Cleveland, OH 44195 USA

[12] Univ Hlth Network, Princess Margaret Canc Ctr, Clin Genom Res Program, Toronto, ON, Canada

[13] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada

[14] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada

[15] Hosp Santa Maria, Ctr Hosp Lisboa Norte, Div Neurosurg, P-1649035 Lisbon, Portugal

[16] Hosp Santa Maria, Ctr Hosp Lisboa Norte, Div Pathol, P-1649035 Lisbon, Portugal

[17] Inst Portugues Oncol Francisco Gentil, Unidade Neurooncol Pediat, P-1099023 Lisbon, Portugal

[18] Univ Childrens Hosp Zurich, Dept Oncol, CH-8032 Zurich, Switzerland

[19] Univ Childrens Hosp Zurich, Dept Neurooncol, CH-8032 Zurich, Switzerland

[20] Univ Pittsburgh, Sch Med, Dept Neurol Surg, Pittsburgh, PA 15224 USA

[21] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA

[22] Baylor Coll Med, Brain Tumor Program, Childrens Canc Ctr, Houston, TX 77030 USA

[23] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[24] Childrens Hosp & Clin Minnesota, Pediat Hematol Oncol, Minneapolis, MN 55404 USA

[25] Univ Utah, Clin Neurosci Ctr, Dept Neurosurg, Salt Lake City, UT 84132 USA

[26] Alfred I DuPont Hosp Children, Wilmington, DE 19803 USA

[27] Kitasato Univ, Sch Med, Dept Neurosurg, Sagamihara, Kanagawa 2520374, Japan

[28] Tohoku Univ, Grad Sch Med, Dept Neurosurg, Sendai, Miyagi 9808574, Japan

[29] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England

[30] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA

[31] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA

[32] Stanford Univ, Sch Med, Dept Neurol Sci, Stanford, CA 94305 USA

[33] Cornell Univ, Weill Med Coll, Dept Pediat, New York, NY 10065 USA

[34] Cornell Univ, Weill Med Coll, Dept Cell Biol, New York, NY 10065 USA

[35] Cornell Univ, Weill Med Coll, Dept Dev Biol, New York, NY 10065 USA

[36] NYU Langone Med Ctr, Dept Neurosurg, New York, NY 10016 USA

[37] Columbia Univ, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY 10032 USA

[38] Rainbow Babies & Childrens Hosp, Dept Pediat Hematol & Oncol, Cleveland, OH 44106 USA

[39] Case Western Reserve, Dept Pediat Hematol & Oncol, Cleveland, OH 44106 USA

[40] Catholic Univ, Sch Med, Pediat Neurosurg, I-00198 Rome, Italy

[41] Univ Munich, Ctr Neuropathol, D-81377 Munich, Germany

[42] Masaryk Univ, Sch Med, Dept Pediat Oncol, Brno 62500, Czech Republic

[43] Univ Paris 05, Necker Enfants Malad Hosp, AP HP, Dept Neurosurg, F-75743 Paris, France

[44] Inst Curie, Signaling Dev & Brain Tumors, CNRS, UMR 3347,INSERM,U1021, F-91405 Orsay 5, France

[45] British Columbia Childrens Hosp, Div Hematol Oncol, Vancouver, BC V6H 3V4, Canada

[46] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, BR-14049900 Sao Paulo, Brazil

[47] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2065, Australia

[48] Childrens Hlth Queensland, Queensland Childrens Med Res Inst, Brisbane, Qld 4029, Australia

[49] Childrens Hlth Queensland, Div Oncol, Brisbane, Qld 4029, Australia

[50] Univ Queensland, UQ Child Hlth Res Ctr, Brisbane, Qld 4029, Australia

来源：

NATURE | 2016年 / 529卷 / 7586期

基金：

美国国家卫生研究院;

关键词：

EVOLUTION; HETEROGENEITY; MUTATIONS; DYNAMICS; IMPACT; MUTAGENESIS; SUBGROUPS; INFERENCE; RELAPSE; CELLS;

D O I：

10.1038/nature16478

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：

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.

引用

页码：351 / +

页数：21

共 59 条

[1] Genetic variegation of clonal architecture and propagating cells in leukaemia
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
[J]. NATURE, 2011, 469 (7330) : 356 - +
[2] EXPANDS: expanding ploidy and allele frequency on nested subpopulations
Andor, Noemi
Harness, Julie V.
Muller, Sabine
Mewes, Hans W.
Petritsch, Claudia
[J]. BIOINFORMATICS, 2014, 30 (01) : 50 - 60
[3] The Implications of Clonal Genome Evolution for Cancer Medicine
Aparicio, Samuel
Caldas, Carlos
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (09) : 842 - 851
[4] Control-FREEC: a tool for assessing copy number and allelic content using next-generation sequencing data
Boeva, Valentina
Popova, Tatiana
Bleakley, Kevin
Chiche, Pierre
Cappo, Julie
Schleiermacher, Gudrun
Janoueix-Lerosey, Isabelle
Delattre, Olivier
Barillot, Emmanuel
[J]. BIOINFORMATICS, 2012, 28 (03) : 423 - 425
[5] Novel Molecular and Computational Methods Improve the Accuracy of Insertion Site Analysis in Sleeping Beauty-Induced Tumors
Brett, Benjamin T.
Berquam-Vrieze, Katherine E.
Nannapaneni, Kishore
Huang, Jian
Scheetz, Todd E.
Dupuy, Adam J.
[J]. PLOS ONE, 2011, 6 (09):
[6] The causes and consequences of genetic heterogeneity in cancer evolution
Burrell, Rebecca A.
McGranahan, Nicholas
Bartek, Jiri
Swanton, Charles
[J]. NATURE, 2013, 501 (7467) : 338 - 345
[7] JAGuaR: Junction Alignments to Genome for RNA-Seq Reads
Butterfield, Yaron S.
Kreitzman, Maayan
Thiessen, Nina
Corbett, Richard D.
Li, Yisu
Pang, Johnson
Ma, Yussanne P.
Jones, Steven J. M.
Birol, Inanc
[J]. PLOS ONE, 2014, 9 (07):
[8] Integrative Genomic Analysis of Medulloblastoma Identifies a Molecular Subgroup That Drives Poor Clinical Outcome
Cho, Yoon-Jae
Tsherniak, Aviad
Tamayo, Pablo
Santagata, Sandro
Ligon, Azra
Greulich, Heidi
Berhoukim, Rameen
Amani, Vladimir
Goumnerova, Liliana
Eberhart, Charles G.
Lau, Ching C.
Olson, James M.
Gilbertson, Richard J.
Gajjar, Amar
Delattre, Olivier
Kool, Marcel
Ligon, Keith
Meyerson, Matthew
Mesirov, Jill P.
Pomeroy, Scott L.
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (11) : 1424 - 1430
[9] Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, Kristian
Lawrence, Michael S.
Carter, Scott L.
Sivachenko, Andrey
Jaffe, David
Sougnez, Carrie
Gabriel, Stacey
Meyerson, Matthew
Lander, Eric S.
Getz, Gad
[J]. NATURE BIOTECHNOLOGY, 2013, 31 (03) : 213 - 219
[10] Cingolani Pablo, 2012, Frontiers in Genetics, V3, P35, DOI 10.3389/fgene.2012.00035

← 1 2 3 4 5 6 →