Longitudinal molecular trajectories of diffuse glioma in adults

被引：387

作者：

Barthel, Floris P. ^{[1
,2
]}

Johnson, Kevin C. ^{[1
]}

Varn, Frederick S. ^{[1
]}

Moskalik, Anzhela D. ^{[1
]}

Tanner, Georgette ^{[3
]}

Kocakavuk, Emre ^{[1
,4
,5
]}

Anderson, Kevin J. ^{[1
]}

Abiola, Olajide ^{[1
]}

Aldape, Kenneth ^{[6
]}

Alfaro, Kristin D. ^{[7
]}

Alpar, Donat ^{[8
,9
]}

Amin, Samirkumar B. ^{[1
]}

Ashley, David M. ^{[10
]}

Bandopadhayay, Pratiti ^{[11
,12
]}

Barnholtz-Sloan, Jill S. ^{[13
]}

Beroukhim, Rameen ^{[12
,14
]}

Bock, Christoph ^{[8
,15
]}

Brastianos, Priscilla K. ^{[16
]}

Brat, Daniel J. ^{[17
]}

Brodbelt, Andrew R. ^{[18
,19
]}

Bruns, Alexander F. ^{[3
]}

Bulsara, Ketan R. ^{[20
]}

Chakrabarty, Aruna ^{[21
]}

Chakravarti, Arnab ^{[22
]}

Chuang, Jeffrey H. ^{[1
,23
]}

Claus, Elizabeth B. ^{[24
,25
]}

Cochran, Elizabeth J. ^{[26
]}

Connelly, Jennifer ^{[27
]}

Costello, Joseph F. ^{[28
]}

Finocchiaro, Gaetano ^{[29
]}

Fletcher, Michael N. ^{[30
]}

French, Pim J. ^{[31
]}

Gan, Hui K. ^{[32
,33
]}

Gilbert, Mark R. ^{[34
]}

Gould, Peter V. ^{[35
]}

Grimmer, Matthew R. ^{[28
]}

Iavarone, Antonio ^{[36
,37
,38
]}

Ismail, Azzam ^{[21
]}

Jenkinson, Michael D. ^{[18
,19
]}

Khasraw, Mustafa ^{[39
]}

Kim, Hoon ^{[1
]}

Kouwenhoven, Mathilde C. M. ^{[40
]}

LaViolette, Peter S. ^{[41
]}

Li, Meihong ^{[1
]}

Lichter, Peter ^{[30
]}

Ligon, Keith L. ^{[12
,42
]}

Lowman, Allison K. ^{[41
]}

Malta, Tathiane M. ^{[43
]}

Mazor, Tali ^{[28
]}

McDonald, Kerrie L. ^{[44
]}

机构：

[1] Jackson Lab Genom Med, Farmington, CT 06032 USA

[2] Vrije Univ Amsterdam, Brain Tumor Ctr Amsterdam, Amsterdam UMC, Dept Pathol, Amsterdam, Netherlands

[3] Univ Leeds, Leeds Inst Med Res St Jamess, Leeds, W Yorkshire, England

[4] Univ Hosp Essen, DKFZ Div Translat Neurooncol, West German Canc Ctr, German Canc Consortium Partner Site, Essen, Germany

[5] Univ Hosp Essen, Dept Neurosurg, Essen, Germany

[6] NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[8] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

[9] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Budapest, Hungary

[10] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC USA

[11] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[12] Broad Inst, Cambridge, MA USA

[13] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Dept Populat & Quantitat Hlth Sci, Cleveland, OH USA

[14] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[15] Med Univ Vienna, Dept Lab Med, Vienna, Austria

[16] Massachusetts Gen Hosp, Div Neurooncol, Boston, MA 02114 USA

[17] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA

[18] Univ Liverpool, Dept Neurosurg, Liverpool, Merseyside, England

[19] Walton Ctr NHS Trust, Liverpool, Merseyside, England

[20] Univ Connecticut, Ctr Hlth, Div Neurosurg, Farmington, CT USA

[21] Leeds Teaching Hosp NHS Trust, Dept Cellular & Mol Pathol, St Jamess Univ Hosp, Leeds, W Yorkshire, England

[22] Arthur G James Canc Hosp, Dept Radiat Oncol, Ohio State Comprehens Canc Ctr, Columbus, OH USA

[23] UConn Hlth, Dept Genet & Genome Sci, Farmington, CT USA

[24] Yale Univ, Sch Publ Hlth, New Haven, CT USA

[25] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA

[26] Med Coll Wisconsin, Dept Pathol & Lab Med, Milwaukee, WI 53226 USA

[27] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA

[28] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA

[29] Fdn IRCCS Ist Neurol Besta, Milan, Italy

[30] German Canc Res Ctr, Heidelberg Ctr Personalized Oncol, German Canc Res Consortium, Div Mol Genet, Heidelberg, Germany

[31] Erasmus MC Univ Med Ctr Rotterdam, Dept Neurol, Rotterdam, Netherlands

[32] Austin Hlth, Olivia Newton John Canc Res Inst, Melbourne, Vic, Australia

[33] La Trobe Univ, Sch Canc Med, Heidelberg, Vic, Australia

[34] NIH, Neurooncol Branch, Bldg 10, Bethesda, MD 20892 USA

[35] Univ Laval, CHU Quebec, Hop Enfants Jesus, Serv Anat Pathol, Quebec City, PQ, Canada

[36] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA

[37] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA

[38] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY USA

[39] Univ Sydney, Cooperat Trials Grp Neurooncol COGNO, NHMRC Clin Trials Ctr, Sydney, NSW, Australia

[40] Vrije Univ Amsterdam, Brain Tumor Ctr Amsterdam, Amsterdam UMC, Dept Neurol, Amsterdam, Netherlands

[41] Med Coll Wisconsin, Dept Radiol, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA

[42] Dana Farber Canc Inst, Dept Oncol Pathol, Boston, MA 02115 USA

[43] Henry Ford Hlth Syst, Henry Ford Canc Inst, Dept Neurosurg, Detroit, MI USA

[44] Univ New South Wales, Cure Brain Canc Biomarkers & Translat Res Grp, Prince Wales Clin Sch, Sydney, NSW, Australia

[45] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurosurg, Seoul, South Korea

[46] Samsung Med Ctr, Inst Refractory Canc Res, Seoul, South Korea

[47] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China

[48] Luxembourg Inst Hlth, Dept Oncol, Luxembourg, Luxembourg

[49] Univ Colorado, Sch Med, Dept Neurosurg, Aurora, CO USA

[50] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Neurosurg, Seoul, South Korea

来源：

NATURE | 2019年 / 576卷 / 7785期

基金：

美国国家卫生研究院; 芬兰科学院; 奥地利科学基金会;

关键词：

CANCER EVOLUTION; GENOMIC ANALYSIS; TUMOR EVOLUTION; WHOLE-GENOME; GLIOBLASTOMA; MUTATIONS; REVEALS; IDH1; HETEROGENEITY; TEMOZOLOMIDE;

D O I：

10.1038/s41586-019-1775-1

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 evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear(12). Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, where as there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar overtime, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrentgliomas. Collectively, our results suggest that the strongest selective pressures occur during earlyglioma development and that current therapies shape this evolution in a largely stochastic manner.

引用

页码：112 / +

页数：28

共 63 条

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← 1 2 3 4 5 6 7 →

共 63 条

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Aldape, Kenneth ;

Amin, Samirkumar B. ;

Ashley, David M. ;

Barnholtz-Sloan, Jill S. ;

Bates, Amanda J. ;

Beroukhim, Rameen ;

Bock, Christoph ;

Brat, Daniel J. ;

Claus, Elizabeth B. ;

Costello, Joseph F. ;

de Groot, John F. ;

Finocchiaro, Gaetano ;

French, Pim J. ;

Gan, Hui K. ;

Griffith, Brent ;

Herold-Mende, Christel C. ;

Horbinski, Craig ;

Iavarone, Antonio ;

Kalkanis, Steven N. ;

Karabatsou, Konstantina ;

Kim, Hoon ;

Kouwenhoven, Mathilde C. M. ;

McDonald, Kerrie L. ;

Miletic, Hrvoje ;

Nam, Do-Hyun ;

Ng, Ho Keung ;

Niclou, Simone P. ;

Noushmehr, Houtan ;

Ormond, D. Ryan ;

Poisson, Laila M. ;

Reifenberger, Guido ;

Roncaroli, Federico ;

Sa, Jason K. ;

Smitt, Peter A. E. Sillevis ;

Smits, Marion ;

Souza, Camila F. ;

Tabatabai, Ghazaleh ;

Van Meir, Erwin G. ;

Verhaak, Roel G. W. ;

Watts, Colin ;

Wesseling, Pieter ;

Woehrer, Adelheid ;

Yung, W. K. Alfred ;

Jungk, Christine ;

Hau, Ann-Christin ;

van Dyck, Eric ;

Westerman, Bait A. ;

Yin, Julia ;

Abiola, Olajide ;

Zeps, Nikolaj .

NEURO-ONCOLOGY, 2018, 20 (07) :873-884

[2] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

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Barthel, Floris P. ;

Wesseling, Pieter ;

Verhaak, Roel G. W. .

ACTA NEUROPATHOLOGICA, 2018, 135 (05) :649-670

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Baumert, Brigitta G. ;

Hegi, Monika E. ;

van den Bent, Martin J. ;

von Deimling, Andreas ;

Gorlia, Thierry ;

Hoang-Xuan, Khe ;

Brandes, Alba A. ;

Kantor, Guy ;

Taphoorn, Martin J. B. ;

Ben Hassel, Mohamed ;

Hartmann, Christian ;

Ryan, Gail ;

Capper, David ;

Kros, Johan M. ;

Kurscheid, Sebastian ;

Wick, Wolfgang ;

Enting, Roelien ;

Reni, Michele ;

Thiessen, Brian ;

Dhermain, Frederic ;

Bromberg, Jacoline E. ;

Feuvret, Loic ;

Reijneveld, Jaap C. ;

Chinot, Olivier ;

Gijtenbeek, Johanna M. M. ;

Rossiter, John P. ;

Dif, Nicolas ;

Balana, Carmen ;

Bravo-Marques, Jose ;

Clement, Paul M. ;

Marosi, Christine ;

Tzuk-Shina, Tzahala ;

Nordal, Robert A. ;

Rees, Jeremy ;

Lacombe, Denis ;

Mason, Warren P. ;

Stupp, Roger .

LANCET ONCOLOGY, 2016, 17 (11) :1521-1532

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Beroukhim, Rameen ;

Getz, Gad ;

Nghiemphu, Leia ;

Barretina, Jordi ;

Hsueh, Teli ;

Linhart, David ;

Vivanco, Igor ;

Lee, Jeffrey C. ;

Huang, Julie H. ;

Alexander, Sethu ;

Du, Jinyan ;

Kau, Tweeny ;

Thomas, Roman K. ;

Shah, Kinial ;

Soto, Horacio ;

Perner, Sven ;

Prensner, John ;

Debiasi, Ralph M. ;

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