doi: 10.1016/j.ccell.2025.11.002.
Epub 2025 Dec 4.
Advancing CNS tumor diagnostics with expanded DNA methylation-based classification
Martin Sill
1
, Daniel Schrimpf
2
, Areeba Patel
3
, Dominik Sturm
4
, Natalie Jäger
5
, Philipp Sievers
2
, Leonille Schweizer
6
, Rouzbeh Banan
2
, David Reuss
2
, Abigail Suwala
2
, Andrey Korshunov
2
, Damian Stichel
2
, Annika K Wefers
7
, Ann-Christin Hau
8
, Henning Boldt
9
, Patrick N Harter
10
, Zied Abdullaev
11
, Jamal Benhamida
12
, Daniel Teichmann
13
, Arend Koch
13
, Jürgen Hench
14
, Stephan Frank
14
, Martin Hasselblatt
15
, Sheila Mansouri
16
, Theresita Díaz de Ståhl
17
, Jonathan Serrano
18
, Jonas Ecker
19
, Florian Selt
20
, Michael Taylor
21
, Vijay Ramaswamy
22
, Florence Cavalli
23
, Anna S Berghoff
24
, Brigitte Bison
25
, Mirjam Blattner-Johnson
26
, Ivo Buchhalter
27
, Rolf Buslei
28
, Gabriele Calaminus
29
, Nicola Dikow
30
, Hildegard Dohmen
31
, Philipp Euskirchen
13
, Gudrun Fleischhack
32
, Amar Gajjar
33
, Nicolas U Gerber
34
, Marco Gessi
35
, Gerrit H Gielen
36
, Astrid Gnekow
37
, Nicholas G Gottardo
38
, Christine Haberler
39
, Stefan Hamelmann
2
, Volkmar Hans
40
, Jordan R Hansford
41
, Christian Hartmann
42
, Frank L Heppner
43
, Pablo Hernaiz Driever
44
, Katja von Hoff
45
, Ulrich W Thomale
46
, Stephan Tippelt
32
, Michael C Frühwald
47
, Christof M Kramm
48
, Ulrich Schüller
49
, Jens Schittenhelm
50
, Martin U Schuhmann
51
, Marco Stein
52
, Petra Ketteler
53
, Marc Ladanyi
12
, Nada Jabado
54
, Barbara C Jones
55
, Chris Jones
56
, Matthias A Karajannis
57
, Ralf Ketter
58
, Patricia Kohlhof
59
, Uwe Kordes
60
, Annekathrin Reinhardt
2
, Christian Kölsche
61
, Katrin Lamszus
62
, Peter Lichter
63
, Sybren L N Maas
64
, Christian Mawrin
65
, Till Milde
66
, Michel Mittelbronn
67
, Camelia-Maria Monoranu
68
, Wolf Mueller
69
, Martin Mynarek
70
, Paul A Northcott
71
, Kristian W Pajtler
72
, Werner Paulus
15
, Arie Perry
73
, Ingmar Blümcke
74
, Karl H Plate
6
, Michael Platten
75
, Matthias Preusser
24
, Torsten Pietsch
76
, Marco Prinz
77
, Guido Reifenberger
78
, Bjarne W Kristensen
79
, Marcel Kool
80
, Volker Hovestadt
81
, David W Ellison
82
, Thomas S Jacques
83
, Pascale Varlet
84
, Nima Etminan
85
, Till Acker
31
, Michael Weller
86
, Christine L White
87
, Olaf Witt
20
, Christel Herold-Mende
88
, Jürgen Debus
89
, Sandro Krieg
90
, Wolfgang Wick
91
, Matija Snuderl
18
, Ken Aldape
11
, Sebastian Brandner
92
, Cynthia Hawkins
93
, Craig Horbinski
94
, Christian Thomas
15
, Pieter Wesseling
95
, Andreas von Deimling
2
, David Capper
13
, Stefan M Pfister
96
, David T W Jones
97
, Felix Sahm
98
Affiliations
Affiliations
- 1 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: m.sill@kitz-heidelberg.de.
- 2 Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 3 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 4 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 5 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
- 6 Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany.
- 7 Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 8 Translational Neuro-Oncology Group, Dr. Senckenbergisches Institute for Neurooncology and Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
- 9 Department of Pathology, Odense University Hospital, Odense, Denmark.
- 10 Bavarian Cancer Research Center (BZKF), Partner Site Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, a partnership between DKFZ and University/University Hospital, LMU Munich, Munich, Germany; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany.
- 11 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
- 12 Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
- 13 Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 14 Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.
- 15 Institute of Neuropathology, University Hospital Münster, Münster, Germany.
- 16 Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.
- 17 Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
- 18 Department of Pathology NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.
- 19 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; KiTZ Clinical Trial Unit, Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
- 20 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
- 21 Department of Pediatrics- Hematology/Oncology, and Neurosurgery, Texas Children's Cancer Center, Hematology-Oncology Section, Baylor College of Medicine, Houston, TX, USA.
- 22 The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON, Canada; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
- 23 Institut Curie, PSL Research University, Paris, France; Inserm, U900, Paris, France; MINES ParisTech, CBIO, Centre for Computational Biology, PSL Research University, 75006 Paris, France.
- 24 Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
- 25 Department of Diagnostic and Interventional Neuroradiology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
- 26 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
- 27 Omics IT and Data Management Core Facility, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
- 28 Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Germany.
- 29 Department of Pediatric Hematology and Oncology, University Hospital Bonn, Bonn, Germany.
- 30 Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.
- 31 Institute of Neuropathology, University of Giessen, Giessen, Germany.
- 32 Pediatrics III, University Hospital Essen, Essen, Germany.
- 33 Division of Neuro Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
- 34 Department of Oncology, University Children's Hospital, Zurich, Switzerland.
- 35 Department of Life Sciences and Public Health, Università Cattolica Sacro Cuore, Rome, Italy.
- 36 Department of Neuropathology, University Hospital Bonn, Bonn, Germany.
- 37 Swabian Children's Cancer Center, Pediatric and Adolescent Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
- 38 Department of Pediatric and Adolescent Oncology/Haematology, Perth Children's Hospital, Nedlands, WA, Australia; Centre for Child Health Research, University of Western Australia, Nedlands, WA, Australia; Brain Tumour Research Program, Telethon Kids Institute, Nedlands, WA, Australia.
- 39 Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
- 40 Department of Neuropathology, Institute for Clinical Pathology, Dietrich-Bonhoeffer-Klinikum, Neubrandenburg, Germany.
- 41 Michael Rice Centre for Hematology and Oncology, Women's and Children's Hospital, South Australia Health and Medical Research Institute, South Australia Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, Australia.
- 42 Department of Neuropathology, Institute of Pathology, Hannover Medical School, Hannover, Germany.
- 43 Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
- 44 Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität Berlin, German HIT-LOGGIC-Registry for Children and Adolescents with Low-Grade Glioma, Department of Pediatric Oncology and Hematology, Berlin, Germany.
- 45 Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
- 46 Pediatric Neurosurgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
- 47 Pediatrics and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg and Bavarian Cancer Research Center/KIONET Bavaria, Augsburg, Bavaria, Germany.
- 48 Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
- 49 Institute of Neuropathology and Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany, Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
- 50 Institute of Neuropathology, Department of Pathology and Neuropathology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
- 51 Section of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital Tübingen, Tübingen, Germany.
- 52 Department of Neurosurgery, Justus-Liebig University, Giessen, Germany.
- 53 Pediatrics III, University Hospital Essen, Essen, Germany; Institute of Human Genetics, University Duisburg-Essen, Essen, Germany.
- 54 Department of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada.
- 55 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
- 56 Division of Molecular Pathology, The Institute of Cancer Research (ICR), Sutton, Surrey, UK.
- 57 Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- 58 Department of Neurosurgery, Saarland University, Medical School, Homburg, Germany.
- 59 Department for Pathology, Katharinenhospital Stuttgart, Stuttgart, Germany.
- 60 Department of Pediatric Hematology/Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
- 61 Institute of Pathology, LMU Munich, Munich, Germany.
- 62 Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 63 National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Division of Molecular Genetics, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
- 64 Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
- 65 Department of Neuropathology, Otto von Guericke University, Magdeburg, Germany.
- 66 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany; Department of Pediatrics, Jena University Hospital and Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany.
- 67 Luxembourg National Center of Pathology (NCP), Laboratoire National de Santé (LNS), Department of Cancer Research (DOCR), Luxembourg Institute of Health (LIH), Luxembourg Centre of Neuropathology (LCNP), Luxembourg Centre for Systems Biomedicine (LCSB), Faculty of Science, Technology and Medicine (FSTM) and Department of Life Sciences and Medicine (DLSM), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- 68 Institute of Pathology, Department of Neuropathology, University of Würzburg, Würzburg, Germany.
- 69 Department of Neuropathology, University of Leipzig, Leipzig, Germany.
- 70 Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pediatric Hematology/Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
- 71 Center of Excellence in Neuro-Oncology Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
- 72 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
- 73 Departments of Pathology and Neurological Surgery, UCSF, San Francisco, CA, USA.
- 74 Department of Neuropathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Partner of the European Reference Network (ERN) EpiCARE, Erlangen, Germany.
- 75 National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translation Neuroscience (MCTN), Heidelberg University, Mannheim, Germany; Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ, Mainz, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
- 76 Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany.
- 77 Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
- 78 Institute of Neuropathology, Medical Faculty, and University Hospital Düsseldorf, Heinrich Heine University, and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany.
- 79 Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark; Department of Pathology, The Bartholin Institute, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
- 80 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; University Medical Center Utrecht, Utrecht, the Netherlands.
- 81 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- 82 Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
- 83 Geoffrey Jefferson Brain Research Centre, Division of Neuroscience, School of Biology, University of Manchester, Manchester, UK.
- 84 Department of Neuropathology, GHU Paris Psychiatry and Neurosciences, Sainte-Anne Hospital, Paris, France.
- 85 Department of Neurosurgery, University Hospital Mannheim, Mannheim, Germany.
- 86 Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
- 87 Victorian Clinical Genetics Services, Parkville, VIC, Australia.
- 88 Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, Medical Faculty Heidelberg, Heidelberg, Germany.
- 89 National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Research in Radiation Oncology (NCRO), Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 90 Department of Neurosurgery, Heidelberg University, Heidelberg, Germany.
- 91 Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 92 Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK; Department of Neurodegenerative Disease, University College London, Institute of Neurology, London, UK.
- 93 The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON, Canada; Division of Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Division of Pathology, Hospital for Sick Children, Toronto, ON, Canada.
- 94 Department of Pathology, Northwestern University, Chicago, IL, USA.
- 95 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology, Amsterdam University Medical Centers/VUmc, Amsterdam, the Netherlands.
- 96 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
- 97 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: david.jones@kitz-heidelberg.de.
- 98 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: felix.sahm@med.uni-heidelberg.de.
- PMID: 41349541
- DOI: 10.1016/j.ccell.2025.11.002
Item in Clipboard
Advancing CNS tumor diagnostics with expanded DNA methylation-based classification
Martin Sill et al.
Cancer Cell.
.
Free article
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doi: 10.1016/j.ccell.2025.11.002.
Epub 2025 Dec 4.
Authors
Martin Sill
1
, Daniel Schrimpf
2
, Areeba Patel
3
, Dominik Sturm
4
, Natalie Jäger
5
, Philipp Sievers
2
, Leonille Schweizer
6
, Rouzbeh Banan
2
, David Reuss
2
, Abigail Suwala
2
, Andrey Korshunov
2
, Damian Stichel
2
, Annika K Wefers
7
, Ann-Christin Hau
8
, Henning Boldt
9
, Patrick N Harter
10
, Zied Abdullaev
11
, Jamal Benhamida
12
, Daniel Teichmann
13
, Arend Koch
13
, Jürgen Hench
14
, Stephan Frank
14
, Martin Hasselblatt
15
, Sheila Mansouri
16
, Theresita Díaz de Ståhl
17
, Jonathan Serrano
18
, Jonas Ecker
19
, Florian Selt
20
, Michael Taylor
21
, Vijay Ramaswamy
22
, Florence Cavalli
23
, Anna S Berghoff
24
, Brigitte Bison
25
, Mirjam Blattner-Johnson
26
, Ivo Buchhalter
27
, Rolf Buslei
28
, Gabriele Calaminus
29
, Nicola Dikow
30
, Hildegard Dohmen
31
, Philipp Euskirchen
13
, Gudrun Fleischhack
32
, Amar Gajjar
33
, Nicolas U Gerber
34
, Marco Gessi
35
, Gerrit H Gielen
36
, Astrid Gnekow
37
, Nicholas G Gottardo
38
, Christine Haberler
39
, Stefan Hamelmann
2
, Volkmar Hans
40
, Jordan R Hansford
41
, Christian Hartmann
42
, Frank L Heppner
43
, Pablo Hernaiz Driever
44
, Katja von Hoff
45
, Ulrich W Thomale
46
, Stephan Tippelt
32
, Michael C Frühwald
47
, Christof M Kramm
48
, Ulrich Schüller
49
, Jens Schittenhelm
50
, Martin U Schuhmann
51
, Marco Stein
52
, Petra Ketteler
53
, Marc Ladanyi
12
, Nada Jabado
54
, Barbara C Jones
55
, Chris Jones
56
, Matthias A Karajannis
57
, Ralf Ketter
58
, Patricia Kohlhof
59
, Uwe Kordes
60
, Annekathrin Reinhardt
2
, Christian Kölsche
61
, Katrin Lamszus
62
, Peter Lichter
63
, Sybren L N Maas
64
, Christian Mawrin
65
, Till Milde
66
, Michel Mittelbronn
67
, Camelia-Maria Monoranu
68
, Wolf Mueller
69
, Martin Mynarek
70
, Paul A Northcott
71
, Kristian W Pajtler
72
, Werner Paulus
15
, Arie Perry
73
, Ingmar Blümcke
74
, Karl H Plate
6
, Michael Platten
75
, Matthias Preusser
24
, Torsten Pietsch
76
, Marco Prinz
77
, Guido Reifenberger
78
, Bjarne W Kristensen
79
, Marcel Kool
80
, Volker Hovestadt
81
, David W Ellison
82
, Thomas S Jacques
83
, Pascale Varlet
84
, Nima Etminan
85
, Till Acker
31
, Michael Weller
86
, Christine L White
87
, Olaf Witt
20
, Christel Herold-Mende
88
, Jürgen Debus
89
, Sandro Krieg
90
, Wolfgang Wick
91
, Matija Snuderl
18
, Ken Aldape
11
, Sebastian Brandner
92
, Cynthia Hawkins
93
, Craig Horbinski
94
, Christian Thomas
15
, Pieter Wesseling
95
, Andreas von Deimling
2
, David Capper
13
, Stefan M Pfister
96
, David T W Jones
97
, Felix Sahm
98
Affiliations
- 1 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: m.sill@kitz-heidelberg.de.
- 2 Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 3 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 4 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 5 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
- 6 Institute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute (FCI), Frankfurt am Main, Germany.
- 7 Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 8 Translational Neuro-Oncology Group, Dr. Senckenbergisches Institute for Neurooncology and Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
- 9 Department of Pathology, Odense University Hospital, Odense, Denmark.
- 10 Bavarian Cancer Research Center (BZKF), Partner Site Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, a partnership between DKFZ and University/University Hospital, LMU Munich, Munich, Germany; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany.
- 11 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
- 12 Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, USA.
- 13 Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 14 Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.
- 15 Institute of Neuropathology, University Hospital Münster, Münster, Germany.
- 16 Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada.
- 17 Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
- 18 Department of Pathology NYU Langone Health and NYU Grossman School of Medicine, New York, NY, USA.
- 19 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; KiTZ Clinical Trial Unit, Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
- 20 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
- 21 Department of Pediatrics- Hematology/Oncology, and Neurosurgery, Texas Children's Cancer Center, Hematology-Oncology Section, Baylor College of Medicine, Houston, TX, USA.
- 22 The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON, Canada; Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
- 23 Institut Curie, PSL Research University, Paris, France; Inserm, U900, Paris, France; MINES ParisTech, CBIO, Centre for Computational Biology, PSL Research University, 75006 Paris, France.
- 24 Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
- 25 Department of Diagnostic and Interventional Neuroradiology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
- 26 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
- 27 Omics IT and Data Management Core Facility, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
- 28 Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Germany.
- 29 Department of Pediatric Hematology and Oncology, University Hospital Bonn, Bonn, Germany.
- 30 Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.
- 31 Institute of Neuropathology, University of Giessen, Giessen, Germany.
- 32 Pediatrics III, University Hospital Essen, Essen, Germany.
- 33 Division of Neuro Oncology, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA.
- 34 Department of Oncology, University Children's Hospital, Zurich, Switzerland.
- 35 Department of Life Sciences and Public Health, Università Cattolica Sacro Cuore, Rome, Italy.
- 36 Department of Neuropathology, University Hospital Bonn, Bonn, Germany.
- 37 Swabian Children's Cancer Center, Pediatric and Adolescent Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
- 38 Department of Pediatric and Adolescent Oncology/Haematology, Perth Children's Hospital, Nedlands, WA, Australia; Centre for Child Health Research, University of Western Australia, Nedlands, WA, Australia; Brain Tumour Research Program, Telethon Kids Institute, Nedlands, WA, Australia.
- 39 Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
- 40 Department of Neuropathology, Institute for Clinical Pathology, Dietrich-Bonhoeffer-Klinikum, Neubrandenburg, Germany.
- 41 Michael Rice Centre for Hematology and Oncology, Women's and Children's Hospital, South Australia Health and Medical Research Institute, South Australia Immunogenomics Cancer Institute, University of Adelaide, Adelaide, SA, Australia.
- 42 Department of Neuropathology, Institute of Pathology, Hannover Medical School, Hannover, Germany.
- 43 Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
- 44 Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität Berlin, German HIT-LOGGIC-Registry for Children and Adolescents with Low-Grade Glioma, Department of Pediatric Oncology and Hematology, Berlin, Germany.
- 45 Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
- 46 Pediatric Neurosurgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
- 47 Pediatrics and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg and Bavarian Cancer Research Center/KIONET Bavaria, Augsburg, Bavaria, Germany.
- 48 Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
- 49 Institute of Neuropathology and Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany, Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
- 50 Institute of Neuropathology, Department of Pathology and Neuropathology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany.
- 51 Section of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital Tübingen, Tübingen, Germany.
- 52 Department of Neurosurgery, Justus-Liebig University, Giessen, Germany.
- 53 Pediatrics III, University Hospital Essen, Essen, Germany; Institute of Human Genetics, University Duisburg-Essen, Essen, Germany.
- 54 Department of Pediatrics, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montreal, QC, Canada.
- 55 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
- 56 Division of Molecular Pathology, The Institute of Cancer Research (ICR), Sutton, Surrey, UK.
- 57 Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- 58 Department of Neurosurgery, Saarland University, Medical School, Homburg, Germany.
- 59 Department for Pathology, Katharinenhospital Stuttgart, Stuttgart, Germany.
- 60 Department of Pediatric Hematology/Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
- 61 Institute of Pathology, LMU Munich, Munich, Germany.
- 62 Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 63 National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Division of Molecular Genetics, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
- 64 Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
- 65 Department of Neuropathology, Otto von Guericke University, Magdeburg, Germany.
- 66 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany; Department of Pediatrics, Jena University Hospital and Comprehensive Cancer Center Central Germany (CCCG), Jena, Germany.
- 67 Luxembourg National Center of Pathology (NCP), Laboratoire National de Santé (LNS), Department of Cancer Research (DOCR), Luxembourg Institute of Health (LIH), Luxembourg Centre of Neuropathology (LCNP), Luxembourg Centre for Systems Biomedicine (LCSB), Faculty of Science, Technology and Medicine (FSTM) and Department of Life Sciences and Medicine (DLSM), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- 68 Institute of Pathology, Department of Neuropathology, University of Würzburg, Würzburg, Germany.
- 69 Department of Neuropathology, University of Leipzig, Leipzig, Germany.
- 70 Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pediatric Hematology/Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
- 71 Center of Excellence in Neuro-Oncology Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
- 72 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany.
- 73 Departments of Pathology and Neurological Surgery, UCSF, San Francisco, CA, USA.
- 74 Department of Neuropathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Partner of the European Reference Network (ERN) EpiCARE, Erlangen, Germany.
- 75 National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translation Neuroscience (MCTN), Heidelberg University, Mannheim, Germany; Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ, Mainz, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
- 76 Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany.
- 77 Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
- 78 Institute of Neuropathology, Medical Faculty, and University Hospital Düsseldorf, Heinrich Heine University, and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany.
- 79 Department of Clinical Medicine and Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark; Department of Pathology, The Bartholin Institute, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
- 80 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; University Medical Center Utrecht, Utrecht, the Netherlands.
- 81 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- 82 Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
- 83 Geoffrey Jefferson Brain Research Centre, Division of Neuroscience, School of Biology, University of Manchester, Manchester, UK.
- 84 Department of Neuropathology, GHU Paris Psychiatry and Neurosciences, Sainte-Anne Hospital, Paris, France.
- 85 Department of Neurosurgery, University Hospital Mannheim, Mannheim, Germany.
- 86 Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
- 87 Victorian Clinical Genetics Services, Parkville, VIC, Australia.
- 88 Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, Medical Faculty Heidelberg, Heidelberg, Germany.
- 89 National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany; Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Research in Radiation Oncology (NCRO), Heidelberg, Germany; Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 90 Department of Neurosurgery, Heidelberg University, Heidelberg, Germany.
- 91 Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neurooncology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 92 Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK; Department of Neurodegenerative Disease, University College London, Institute of Neurology, London, UK.
- 93 The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON, Canada; Division of Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada; Division of Pathology, Hospital for Sick Children, Toronto, ON, Canada.
- 94 Department of Pathology, Northwestern University, Chicago, IL, USA.
- 95 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Pathology, Amsterdam University Medical Centers/VUmc, Amsterdam, the Netherlands.
- 96 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University Hospital, Heidelberg, Germany.
- 97 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: david.jones@kitz-heidelberg.de.
- 98 Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: felix.sahm@med.uni-heidelberg.de.
- PMID: 41349541
- DOI: 10.1016/j.ccell.2025.11.002
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Abstract
DNA methylation-based classification is now central to contemporary neuro-oncology, as highlighted by the World Health Organization (WHO) classification of central nervous system (CNS) tumors. We present the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.8), trained on 7,495 methylation profiles, which expands recognized entities from 91 classes in version 11 (v11) to 184 subclasses. This expansion is a result of newly identified tumor types discovered through our large online repository and global collaborations, underscoring CNS tumor heterogeneity. The random forest-based classifier achieves 95% subclass-level accuracy, with its well-calibrated probabilistic scores providing a reliable measure of confidence for each classification. Its hierarchical output structure enables interpretation across subclass, class, family, and superfamily levels, thereby supporting clinical decisions at multiple granularities. Comparative analyses demonstrate that v12.8 surpasses previous versions and conventional WHO-based approaches. These advances highlight the improved precision and practical utility of the updated classifier in personalized neuro-oncology.
Keywords: CNS tumors; DNA methylation; MLOps; artificial intelligence; classification; epigenetics; machine learning; molecular diagnostics; precision medicine; tumor heterogeneity.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests M. Sill, D.S., M. Snuderl, A.v.D., S.M.P., D.C., D.T.W.J., and F.S. are co-founders and shareholders of Heidelberg Epignostix GmbH, a company that develops and commercializes DNA methylation-based classifiers for CNS and other tumors, including the Heidelberg CNS Classifier described in this manuscript. M. Sill and N.J. became full-time employees of Heidelberg Epignostix in July 2024, A.P. in December 2024, and D.S. became a part-time employee in November 2024. M. Sill, A.v.D., D.S., D.T.W.J., D.C., V.H., and S.M.P. report patent EP16710700.2 and EP4384959A2. These patents cover the intellectual property for the DNA methylation-based CNS tumor classification method, which is the specific technology described and advanced in this manuscript. M.A.K. was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center. G.F. and S.T. were funded by the DKS2020.02 research grant for HIT-REZ-Registry, German Childhood Cancer Foundation. M.W. has received research grants from Novartis, Quercis, and Versameb, and honoraria for lectures, advisory boards, or consulting from Anheart, Bayer, Curevac, Medac, Neurosense, Novartis, Novocure, Orbus, Pfizer, Philogen, Roche, and Servier. M. Snuderl is supported by NINDS grant R01-NS122987 and is scientific advisor/shareholder of Halo Dx, and advisor to Arima Genomics and InnoSIGN, and has received research funding from Lilly USA. The German HIT-LOGGIC-Registry was supported by the Deutsche Kinderkrebsstiftung (DKKS 2019.06, 2021.03, and 2023.08). The protocol was approved by the IRB (EA2/030/19). P.H.D. is member of the Alexion Advisory Board on behalf of Charité-Universitätsmedizin Berlin. M.P. has received honoraria for lectures, consultation, or advisory board participation from Bayer, Bristol-Myers Squibb, Novartis, GLG, CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, Boehringer-Ingelheim, Telix, Medscape, OncLive, Medac, Nerviano Medical Sciences, and ITM Oncologics GmbH. A.S.B. has research support from Daiichi Sankyo and Roche, and honoraria from Roche, Bristol-Myers Squibb, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa, Seagen, Alexion, and Servier, as well as travel support from Roche, Amgen, and AbbVie.
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Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.Sill M, Schrimpf D, Patel A, Sturm D, Jäger N, Sievers P, Schweizer L, Banan R, Reuss D, Suwala A, Korshunov A, Stichel D, Wefers AK, Hau AC, Boldt H, Harter PN, Abdullaev Z, Benhamida J, Teichmann D, Koch A, Hench J, Frank S, Hasselblatt M, Mansouri S, Díaz de Ståhl T, Serrano J, Ecker J, Selt F, Taylor M, Ramaswamy V, Cavalli F, Berghoff AS, Bison B, Blattner-Johnson M, Buchhalter I, Buslei R, Calaminus G, Dikow N, Dohmen H, Euskirchen P, Fleischhack G, Gajjar A, Gerber NU, Gessi M, Gielen GH, Gnekow A, Gottardo NG, Haberler C, Hamelmann S, Hans V, Hansford JR, Hartmann C, Heppner FL, Driever PH, von Hoff K, Thomale UW, Tippelt S, Frühwald MC, Kramm CM, Schüller U, Schittenhelm J, Schuhmann MU, Stein M, Ketteler P, Ladanyi M, Jabado N, Jones BC, Jones C, Karajannis MA, Ketter R, Kohlhof P, Kordes U, Reinhardt A, Kölsche C, Lamszus K, Lichter P, Maas SLN, Mawrin C, Milde T, Mittelbronn M, Monoranu CM, Mueller W, Mynarek M, Northcott PA, Pajtler KW, Paulus W, Perry A, Blümcke I, Plate KH, Platten M, Preusser M, Pietsch T, Prinz M, Reifenberger G, Kristensen BW, Kool M, Hovestadt V, Ellison DW, Jacques TS, Varlet P, Etminan N, Acker T, Weller M, White CL, Witt O, Herold-Mende C, De… See abstract for full author list ➔ Sill M, et al. medRxiv [Preprint]. 2025 May 29:2025.05.28.25328344. doi: 10.1101/2025.05.28.25328344. medRxiv. 2025. Update in: Cancer Cell. 2026 Feb 9;44(2):340-354.e2. doi: 10.1016/j.ccell.2025.11.002. PMID: 40492071 Free PMC article. Updated. Preprint.
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Advancing sarcoma diagnostics with expanded DNA methylation-based classification.Jäger N, Reuss DE, Sill M, Schrimpf D, Suwala AK, Sievers P, Banan R, Hinz F, Rahmanzade R, Bogumil H, Aras KF, Patel A, Korshunov A, Bewerunge-Hudler M, Cleven AH, Esteller M, Glimm H, Hartmann W, Kreutzfeld S, Heilig C, Milde T, Petersen I, Vokuhl CM, Wick W, Witt O, Kervarrec T, Miele E, Serrano J, Frank S, Kashofer K, Leer AM, Pfaff E, Pages M, Tauziede-Espariat A, Toberer F, Boldt HB, Martinek P, Brandner S, Euzebio M, Siegfried A, Chalker J, Harter P, Appay R, Dietmaier W, Hasselblatt M, Flucke UE, Hiemcke-Jiwa LS, Solomon D, Frydrychowicz C, Varlet P, Goeppert B, Nathrath M, Blattmann C, Sparber-Sauer M, Kolb A, Mittelbronn M, Mentzel T, Leisz S, Harder A, Acker T, Pratt D, Wardelmann E, Benhamida J, Ladanyi M, Jurmeister P, Foulkes W, Ajuyah P, Ziegler DZ, Hench J, Nederkoorn MJ, Versleijen-Jonkers YM, Mechtersheimer G, Krieg S, Gessler M, Baumhoer D, Behjati S, Bertero L, Griwank K, Schadendorf D, Hogendoorn PC, Emile JF, Kemps PG, Jarosch A, Ronellenfitsch MW, Idler TS, Aust D, Herold S, Pablik J, Al-Hussaini M, Abdullaev Z, Yeung M, Wachtel M, Brack E, Kommoss FK, Miettinen M, Aldape K, Flanagan AM, Dirksen U, Pajtler K, Grünewald TG, Lipka D, Fröhling S, Koelsche C, Sn… See abstract for full author list ➔ Jäger N, et al. medRxiv [Preprint]. 2025 Jun 30:2025.06.30.25330543. doi: 10.1101/2025.06.30.25330543. medRxiv. 2025. Update in: Cancer Cell. 2026 Feb 9;44(2):340-354.e2. doi: 10.1016/j.ccell.2025.11.002. PMID: 40630595 Free PMC article. Updated. Preprint.
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