DNA methylation-based classification of central nervous system tumours

被引：2028

作者：

Capper, David ^{[1
,2
,3
,4
,5
]}

Jones, David T. W. ^{[6
,7
]}

Sill, Martin ^{[6
,7
,8
]}

Hovestadt, Volker ^{[9
,124
,125
,126
]}

Schrimpf, Daniel ^{[1
,2
]}

Sturm, Dominik ^{[6
,7
,10
]}

Koelsche, Christian ^{[1
,2
]}

Sahm, Felix ^{[1
,2
]}

Chavez, Lukas ^{[6
,7
]}

Reuss, David E. ^{[1
,2
]}

Kratz, Annekathrin ^{[1
,2
]}

Wefers, Annika K. ^{[1
,2
]}

Huang, Kristin ^{[1
,2
]}

Pajtler, Kristian W. ^{[6
,7
,10
]}

Schweizer, Leonille ^{[1
,4
]}

Stichel, Damian ^{[1
,2
]}

Olar, Adriana ^{[11
,12
,13
]}

Engel, Nils W. ^{[14
,15
]}

Lindenberg, Kerstin ^{[2
]}

Harter, Patrick N. ^{[16
,17
]}

Braczynski, Anne K. ^{[16
,17
]}

Plate, Karl H. ^{[16
,17
]}

Dohmen, Hildegard ^{[18
]}

Garvalov, Boyan K. ^{[18
]}

Coras, Roland ^{[19
]}

Hoelsken, Annett ^{[19
]}

Hewer, Ekkehard ^{[20
]}

Bewerunge-Hudler, Melanie ^{[21
]}

Schick, Matthias ^{[21
]}

Fischer, Roger ^{[21
]}

Beschorner, Rudi ^{[22
]}

Schittenhelm, Jens ^{[22
]}

Staszewski, Ori ^{[23
]}

Wani, Khalida ^{[24
]}

Varlet, Pascale ^{[25
]}

Pages, Melanie ^{[25
]}

Temming, Petra ^{[26
]}

Lohmann, Dietmar ^{[27
]}

Selt, Florian ^{[6
,10
,28
,29
]}

Witt, Hendrik ^{[6
,7
,10
]}

Milde, Till ^{[6
,10
,28
,29
]}

Witt, Olaf ^{[6
,10
,28
,29
]}

Aronica, Eleonora ^{[30
,31
,32
]}

Giangaspero, Felice ^{[33
,34
]}

Rushing, Elisabeth ^{[35
]}

Scheurlen, Wolfram ^{[36
]}

Geisenberger, Christoph ^{[37
,38
]}

Rodriguez, Fausto J. ^{[39
]}

Becker, Albert ^{[40
]}

Preusser, Matthias ^{[41
]}

机构：

[1] Univ Hosp Heidelberg, Dept Neuropathol, Heidelberg, Germany

[2] German Canc Res Ctr, German Canc Consortium DKTK, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[3] Charite, Humboldt Univ Berlin, Freie Univ Berlin, Berlin, Germany

[4] Berlin Inst Hlth, Dept Neuropathol, Berlin, Germany

[5] German Canc Res Ctr, German Canc Consortium DKTK, Partner Site Berlin, Heidelberg, Germany

[6] NCT Heidelberg KiTZ, Hopp Childrens Canc Ctr, Heidelberg, Germany

[7] German Canc Res Ctr, Div Pediat Neurooncol, German Canc Consortium DKTK, Heidelberg, Germany

[8] German Canc Res Ctr, Div Biostat, Heidelberg, Germany

[9] German Canc Res Ctr, Div Mol Genet, Heidelberg, Germany

[10] Univ Hosp Heidelberg, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[11] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA

[12] Med Univ South Carolina, Dept Neurosurg, Charleston, SC 29425 USA

[13] Hollings Canc Ctr, Charleston, SC 29425 USA

[14] Univ Med Ctr Hamburg, Dept Oncol & Hematol, Sect Bone Marrow Transplant & Pneumol, Hubertus Wald Tumorzentrum,Univ Canc Ctr Hamburg, Hamburg, Germany

[15] Ludwig Maximilians Univ Munchen, Ctr Neuropathol & Prion Res, Munich, Germany

[16] Goethe Univ Frankfurt Main, Inst Neurol, Edinger Inst, Frankfurt, Germany

[17] German Canc Res Ctr, Partner Site Frankfurt Mainz, German Canc Consortium DKTK, Heidelberg, Germany

[18] Univ Giessen, Inst Neuropathol, Giessen, Germany

[19] Friedrich Alexander Univ Erlangen Nuremberg, Univ Hosp Erlangen, Neuropathol Inst, Erlangen, Germany

[20] Univ Bern, Inst Pathol, Bern, Switzerland

[21] German Canc Res Ctr, Genom & Prote Core Facil, Heidelberg, Germany

[22] Univ Hosp Tubingen, Dept Neuropathol, Inst Pathol & Neuropathol, Tubingen, Germany

[23] Univ Freiburg, Med Ctr, Inst Neuropathol, Fac Med, Freiburg, Germany

[24] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

[25] Univ Paris, Ctr Hosp St Anne, Dept Neuropathol, Paris, France

[26] Univ Hosp Essen, Pediat 3, Pediat Oncol & Hematol, Essen, Germany

[27] Univ Duisburg Essen, Eye Canc Res Grp, Fac Med, Essen, Germany

[28] German Canc Res Ctr, CCU Pediat Oncol G340, Heidelberg, Germany

[29] German Canc Consortium DKTK, Heidelberg, Germany

[30] Univ Amsterdam, Dept Neuropathol, AMC, Amsterdam, Netherlands

[31] Univ Amsterdam, Swammerdam Inst Life Sci, Ctr Neurosci, Amsterdam, Netherlands

[32] SEIN, Amsterdam, Netherlands

[33] Sapienza Univ, Dept Radiol Oncol & Anatomopathol Sci, Rome, Italy

[34] IRCCS Neuromed, Pozzilli, Italy

[35] Univ Hosp Zurich, Dept Neuropathol, Zurich, Switzerland

[36] Cnopfsche Kinderklin Nuremberg, Nurnberg, Germany

[37] Heidelberg Univ Hosp, Dept Neurosurg, Heidelberg, Germany

[38] Hubrecht Inst KNAW Royal Netherlands Acad Arts &, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands

[39] Johns Hopkins Univ, Sch Med, Div Neuropathol, Baltimore, MD USA

[40] Univ Bonn, Dept Neuropathol, Bonn, Germany

[41] Med Univ Vienna, Dept Med 1, Comprehens Canc Ctr Vienna, CNS Unit CCC CNS, Vienna, Austria

[42] Med Univ Vienna, Inst Neurol, Vienna, Austria

[43] Univ Bergen, Dept Biomed, Bergen, Norway

[44] Luxembourg Inst Hlth, Dept Oncol, NORLUX Neurooncol Lab, Luxembourg, Luxembourg

[45] Beaumont Hosp, Dept Neuropathol, Dublin, Ireland

[46] Univ Hosp Cologne, Dept Neuropathol, Cologne, Germany

[47] Basel Univ Hosp, Inst Pathol, Dept Neuropathol, Basel, Switzerland

[48] NYU, Langone Med Ctr, New York, NY USA

[49] Univ Med Ctr Gottingen, Inst Neuropathol, Gottingen, Germany

[50] Luzerner Kantonsspital, Div Oncol, Luzern, Switzerland

来源：

NATURE | 2018年 / 555卷 / 7697期

基金：

俄罗斯科学基金会;

关键词：

CLASS PROBABILITY ESTIMATION; MOLECULAR CLASSIFICATION; MEDULLOBLASTOMA; MULTICENTER; EXPRESSION; SUBGROUPS; COMPRISE; SUBSETS; GLIOMAS;

D O I：

10.1038/nature26000

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：

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challengingwith substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

引用

页码：469 / +

页数：26

共 53 条

[41]

[42] Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities [J].

Reuss, David E. ;

Kratz, Annekathrin ;

Sahm, Felix ;

Capper, David ;

Schrimpf, Daniel ;

Koelsche, Christian ;

Hovestadt, Volker ;

Bewerunge-Hudler, Melanie ;

Jones, David T. W. ;

Schittenhelm, Jens ;

Mittelbronn, Michel ;

Rushing, Elisabeth ;

Simon, Matthias ;

Westphal, Manfred ;

Unterberg, Andreas ;

Platten, Michael ;

Paulus, Werner ;

Reifenberger, Guido ;

Tonn, Joerg-Christian ;

Aldape, Kenneth ;

Pfister, Stefan M. ;

Korshunov, Andrey ;

Weller, Michael ;

Herold-Mende, Christel ;

Wick, Wolfgang ;

Brandner, Sebastian ;

von Deimling, Andreas .

ACTA NEUROPATHOLOGICA, 2015, 130 (03) :407-417

[43] Next-generation sequencing in routine brain tumor diagnostics enables an integrated diagnosis and identifies actionable targets [J].

Sahm, Felix ;

Schrimpf, Daniel ;

Jones, David T. W. ;

Meyer, Jochen ;

Kratz, Annekathrin ;

Reuss, David ;

Capper, David ;

Koelsche, Christian ;

Korshunov, Andrey ;

Wiestler, Benedikt ;

Buchhalter, Ivo ;

Milde, Till ;

Selt, Florian ;

Sturm, Dominik ;

Kool, Marcel ;

Hummel, Manuela ;

Bewerunge-Hudler, Melanie ;

Mawrin, Christian ;

Schueller, Ulrich ;

Jungk, Christine ;

Wick, Antje ;

Witt, Olaf ;

Platten, Michael ;

Herold-Mende, Christel ;

Unterberg, Andreas ;

Pfister, Stefan M. ;

Wick, Wolfgang ;

von Deimling, Andreas .

ACTA NEUROPATHOLOGICA, 2016, 131 (06) :903-910

[44] Class probability estimation for medical studies [J].

Simon, Richard .

BIOMETRICAL JOURNAL, 2014, 56 (04) :597-600

[45]

Smola A. J., 2000, Advances in large margin classifiers

[46] A systematic analysis of performance measures for classification tasks [J].

Sokolova, Marina ;

Lapalme, Guy .

INFORMATION PROCESSING & MANAGEMENT, 2009, 45 (04) :427-437

[47] New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs [J].

Sturm, Dominik ;

Orr, Brent A. ;

Toprak, Umut H. ;

Hovestadt, Volker ;

Jones, David T. W. ;

Capper, David ;

Sill, Martin ;

Buchhalter, Ivo ;

Northcott, Paul A. ;

Leis, Irina ;

Ryzhova, Marina ;

Koelsche, Christian ;

Pfaff, Elke ;

Allen, Sariah J. ;

Balasubramanian, Gnanaprakash ;

Worst, Barbara C. ;

Pajtler, Kristian W. ;

Brabetz, Sebastian ;

Johann, Pascal D. ;

Sahm, Felix ;

Reimand, Jueri ;

Mackay, Alan ;

Carvalho, Diana M. ;

Remke, Marc ;

Phillips, Joanna J. ;

Perry, Arie ;

Cowdrey, Cynthia ;

Drissi, Rachid ;

Fouladi, Maryam ;

Giangaspero, Felice ;

Lastowska, Maria ;

Grajkowska, Wieslawa ;

Scheurlen, Wolfram ;

Pietsch, Torsten ;

Hagel, Christian ;

Gojo, Johannes ;

Loetsch, Daniela ;

Berger, Walter ;

Slavc, Irene ;

Haberler, Christine ;

Jouvet, Anne ;

Holm, Stefan ;

Hofer, Silvia ;

Prinz, Marco ;

Keohane, Catherine ;

Fried, Iris ;

Mawrin, Christian ;

Scheie, David ;

Mobley, Bret C. ;

Schniederjan, Matthew J. .

CELL, 2016, 164 (05) :1060-1072

[48] Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma [J].

Sturm, Dominik ;

Witt, Hendrik ;

Hovestadt, Volker ;

Dong-Anh Khuong-Quang ;

Jones, David T. W. ;

Konermann, Carolin ;

Pfaff, Elke ;

Toenjes, Marge ;

Sill, Martin ;

Bender, Sebastian ;

Kool, Marcel ;

Zapatka, Marc ;

Becker, Natalia ;

Zucknick, Manuela ;

Hielscher, Thomas ;

Liu, Xiao-Yang ;

Fontebasso, Adam M. ;

Ryzhova, Marina ;

Albrecht, Steffen ;

Jacob, Karine ;

Wolter, Marietta ;

Ebinger, Martin ;

Schuhmann, Martin U. ;

van Meter, Timothy ;

Fruehwald, Michael C. ;

Hauch, Holger ;

Pekrun, Arnulf ;

Radlwimmer, Bernhard ;

Niehues, Tim ;

von Komorowski, Gregor ;

Duerken, Matthias ;

Kulozik, Andreas E. ;

Madden, Jenny ;

Donson, Andrew ;

Foreman, Nicholas K. ;

Drissi, Rachid ;

Fouladi, Maryam ;

Scheurlen, Wolfram ;

von Deimling, Andreas ;

Monoranu, Camelia ;

Roggendorf, Wolfgang ;

Herold-Mende, Christel ;

Unterberg, Andreas ;

Kramm, Christof M. ;

Felsberg, Joerg ;

Hartmann, Christian ;

Wiestler, Benedikt ;

Wick, Wolfgang ;

Milde, Till ;

Witt, Olaf .

CANCER CELL, 2012, 22 (04) :425-437

[49] Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups [J].

Thomas, Christian ;

Sill, Martin ;

Ruland, Vincent ;

Witten, Anika ;

Hartung, Stefan ;

Kordes, Uwe ;

Jeibmann, Astrid ;

Beschorner, Rudi ;

Keyvani, Kathy ;

Bergmann, Markus ;

Mittelbronn, Michel ;

Pietsch, Torsten ;

Felsberg, Joerg ;

Monoranu, Camelia M. ;

Varlet, Pascale ;

Hauser, Peter ;

Olar, Adriana ;

Grundy, Richard G. ;

Wolff, Johannes E. ;

Korshunov, Andrey ;

Jones, David T. ;

Bewerunge-Hudler, Melanie ;

Hovestadt, Volker ;

von Deimling, Andreas ;

Pfister, Stefan M. ;

Paulus, Werner ;

Capper, David ;

Hasselblatt, Martin .

NEURO-ONCOLOGY, 2016, 18 (06) :790-796

[50] Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician's perspective [J].

van den Bent, Martin J. .

ACTA NEUROPATHOLOGICA, 2010, 120 (03) :297-304

← 1 2 3 4 5 6 →