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Articles by Philipp Sievers
Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification
Abstract Meningiomas in pediatric and adolescent/young adult patients are poorly characterized biologically and clinically, and risk stratification is largely extrapolated from adult tumors. We analyze 293 tumors from patients aged 0–39 years using integrated histopathological and molecular profiling.
Hetairos is a histology-based artificial intelligence model for predicting central nervous system tumor methylation subtypes
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Abstract Molecular testing is essential for classifying central nervous system (CNS) tumors, with methylation profiling providing the highest diagnostic granularity. However, this requires more resources and time than conventional hematoxylin and eosin (H&E) histopathology, which is widely available globally. Here we propose Hetairos, an artificial intelligence algorithm that predicts 102 methylation-based CNS tumor subtypes from digital H&E slides.
By Darui Jin, Artem Shmatko, Areeba Patel, Samuel Rutz, Lukas Friedrich, Rouzbeh Banan, Ramin Rahmanzade, Philipp Sievers, Stefan Hamelmann, Daniel Schrimpf, Kirsten Göbel, Sybren L. N. Maas, Martin Sill, Felix Hinz, Abigail K. Suwala, Felix Keller, Antje Habel, Gleb D. Rukhovich, Ferdinand Zettl, Obada T. Alhalabi, Sebastian Ille, Jannik Sehring, Daniel Amsel, Benedikt Wiestler, Pedro Lago, Bogdana Suchorska, Dominik Sturm, David E. Reuss, Pieter Wesseling, Frank L. Heppner, Ingmar Blümcke, Claire Delbridge, Martin Jakobs, Christel Herold-Mende, Sandro M. Krieg, Wolfgang Wick, David Jones, Stefan M. Pfister, Maysa Al-Hussaini, Yanghao Hou, Felipe D’Almeida Costa, Leonille Schweizer, Luca Bertero, Arnault Tauziède-Espariat, Pascale Varlet, Doron Merkler, Kristof Egervari, Hildegard Dohmen, Roger Gejman, Sebastian Brandner, Xiangzhi Bai, Andreas von Deimling, Felix Sahm, Moritz Gerstung, Henri Bogumil, Olfat Ahmad, Adelheid Wöhrer, Pablo Zoroquiain
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Nature
Verified
Turn-on luminescence from molecular rotor realignment in metal-organic framework thin films
Abstract Sub-unit motion within metal-organic frameworks (MOFs) offers unique opportunities for nanoscale sensing. However, achieving controlled partial rotation of bulky linkers remains a significant challenge. In this study, a 50-fold luminescence enhancement is observed from a MOF thin film when intra-pore solvent flow orients the linker chromophores. These MOF thin films can be prepared via a facile drop-casting method on various substrates.
A microenvironment-determined risk continuum refines subtyping in meningioma and reveals determinants of machine learning-based tumor classification - Nature Genetics
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Abstract Classification of tumors in neuro-oncology today relies on molecular patterns (mostly DNA methylation) and their machine learning-supported interpretation. Understanding the process of algorithmic interpretation is essential for safe application in clinical routine. This is paradigmatically true for the most common primary intracranial tumor in adults, meningioma.
By Yiheng Tang, Ferdinand Zettl, Salvatore Benfatto, Martin Sill, Yahaya A. Yabo, Matthieu Peyre, Roman Sankowski, Philipp Sievers, C. Oliver Hanemann, Christian Mawrin, Olivier Ayrault, Michael Platten, Tim Kacprowski, Markus List, Jan Baumbach, Miriam Ratliff, Jan-Philipp Mallm, Eelke M Bos, Marco Prinz, Michael Weller, Felix J. Hartmann, Matthias Preusser, Christel Herold-Mende, Sandro M. Krieg, Stefan M. Pfister, Wolfgang Wick, Andreas von Deimling, Dieter Henrik Heiland, Volker Hovestadt, Moritz Gerstung, Matthias Schlesner, Christina Blume, Domenico Calafato, Helin Kardo
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Nature
Verified
A microenvironment-determined risk continuum refines subtyping in meningioma and reveals determinants of machine learning-based tumor classification
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Oncologists Are Begging People To Take This One Common Cancer Risk Factor Seriously We’re not thinking or talking about this one enough. No one gets cancer on purpose. Yet, it’s hard to find someone who the disease hasn’t touched, …
By Yiheng Tang, Eric Y. Stutheit-Zhao, Ramin Rahmanzade, Christina Blume, Thomas Hielscher, Ferdinand Zettl, Salvatore Benfatto, Domenico Calafato, Martin Sill, Yahaya A. Yabo, Felix Behling, Abigail K. Suwala, Helin Kardo, Michael Ritter, Matthieu Peyre, Roman Sankowski, Konstantin Okonechnikov, Philipp Sievers, Areeba Patel, David E. Reuss, Mirco Friedrich, Damian Stichel, Daniel Schrimpf, Katja Beck, Hans-Georg Wirsching, Gerhard Jungwirth, C. Oliver Hanemann, Katrin Lamszus, Nima Etminan, Andreas W. Unterberg, Christian Mawrin, Olivier Ayrault, Peter Lichter, Guido Reifenberger, Michael Platten, Tim Kacprowski, Markus List, Josch K. Pauling, Jan Baumbach, Zvi Ram, Miriam Ratliff, Jan-Philipp Mallm, Marian C. Neidert, Eelke M Bos, Marco Prinz, Michael Weller, Felix J. Hartmann, Matthias Preusser, Ghazaleh Tabatabai, Christel Herold-Mende, Sandro M. Krieg, Stefan M. Pfister, Wolfgang Wick, Michel Kalamarides, Andreas von Deimling, Dieter Henrik Heiland, Volker Hovestadt, Moritz Gerstung, Matthias Schlesner, Felix Sahm, Jasim Kada Benotmane, Rachel Grossmann
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Flipboard
Advancing CNS tumor diagnostics with expanded DNA methylation-based classification
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ArticleVolume 44, Issue 2p340-354.e2Open access 1Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany 2Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany 3Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany 4Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany...
By Martin Sill, Daniel Schrimpf, Areeba Patel, Dominik Sturm, Natalie Jäger, Philipp Sievers, Leonille Schweizer, Rouzbeh Banan, David E. Reuss, Abigail K. Suwala, Andrey Korshunov, Damian Stichel, Annika K Wefers, Ann-Christin Hau, Henning Boldt, Patrick N. Harter, Zied Abdullaev, Jamal Benhamida, Daniel Teichmann, Arend Koch, Jürgen Hench, Stephan Frank, Martin Hasselblatt, Sheila Mansouri, Jonathan Serrano, Jonas Ecker, Florian Selt, Michael Taylor Verified, Vijay Ramaswamy, Anna S. Berghoff, Brigitte Bison, Mirjam Blattner-Johnson, Ivo Buchhalter, Rolf Buslei, Gabriele Calaminus, Nicola Dikow, Hildegard Dohmen, Philipp Euskirchen, Gudrun Fleischhack, Amar Gajjar, Nicolas U. Gerber, Marco Gessi, Gerrit H. Gielen, Astrid K. Gnekow, Nicholas G Gottardo, Christine Haberler, Stefan Hamelmann, Volkmar Hans, Jordan Hansford, Christian Hartmann, Frank L. Heppner, Pablo Hernáiz Driever, Katja von Hoff, Ulrich W. Thomale, Stephan Tippelt, Michael C. Frühwald, Christof M. Kramm, Ulrich Schüller, Jens Schittenhelm, Martin Schuhmann, Marco Stein, Petra Ketteler, Marc Ladanyi, Nada Jabado, Barbara Jones, Chris Jones, Matthias A. Karajannis, Ralf Ketter, Patricia Kohlhof, Uwe Kordes, Annekathrin Reinhardt, Christian Kölsche, Katrin Lamszus, Peter Lichter, Sybren L.N. Maas, Christian Mawrin, Michel Mittelbronn, Camelia-Maria Monoranu, Wolf Mueller, Martin Mynarek, Paul A. Northcott, Kristian W. Pajtler, Werner Paulus, Arie Perry, Ingmar Blümcke, Karl H. Plate, Michael Platten, Matthias Preusser, Torsten Pietsch, Marco Prinz, Guido Reifenberger, Bjarne W. Kristensen, Marcel Kool, Volker Hovestadt, David Ellison, Thomas Jacques, Pascale Varlet, Nima Etminan, Michael Weller, Christine White, Olaf Witt, Christel Herold-Mende, Jürgen Debus, Sandro M. Krieg, Wolfgang Wick, Matija Snuderl, Ken Aldape, Sebastian Brandner, Cynthia Hawkins, Craig M Horbinski, Christian Thomas, Pieter Wesseling, Andreas von Deimling, David Capper, Stefan M. Pfister, Felix Sahm
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Cell Press
Verified
Advancing CNS tumor diagnostics with expanded DNA methylation-based classification
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ArticleOnline nowOpen access 1Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany 2Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany 3Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany 4Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany 5Division of Pediatric...
By Martin Sill, Daniel Schrimpf, Areeba Patel, Dominik Sturm, Natalie Jäger, Philipp Sievers, Leonille Schweizer, Rouzbeh Banan, David E. Reuss, Abigail K. Suwala, Andrey Korshunov, Damian Stichel, Annika K Wefers, Ann-Christin Hau, Henning Boldt, Patrick N. Harter, Zied Abdullaev, Jamal Benhamida, Daniel Teichmann, Arend Koch, Jürgen Hench, Stephan Frank, Martin Hasselblatt, Sheila Mansouri, Jonathan Serrano, Jonas Ecker, Michael Taylor Verified, Vijay Ramaswamy, Anna S. Berghoff, Brigitte Bison, Mirjam Blattner-Johnson, Ivo Buchhalter, Gabriele Calaminus, Nicola Dikow, Hildegard Dohmen, Philipp Euskirchen, Gudrun Fleischhack, Amar Gajjar, Nicolas U. Gerber, Marco Gessi, Gerrit H. Gielen, Astrid K. Gnekow, Nicholas G Gottardo, Christine Haberler, Stefan Hamelmann, Jordan Hansford, Christian Hartmann, Frank L. Heppner, Pablo Hernáiz Driever, Katja von Hoff, Ulrich W. Thomale, Michael C. Frühwald, Christof M. Kramm, Ulrich Schüller, Jens Schittenhelm, Martin Schuhmann, Marco Stein, Petra Ketteler, Marc Ladanyi, Nada Jabado, Barbara Jones, Chris Jones, Matthias A. Karajannis, Uwe Kordes, Annekathrin Reinhardt, Christian Kölsche, Katrin Lamszus, Peter Lichter, Sybren L.N. Maas, Christian Mawrin, Michel Mittelbronn, Camelia-Maria Monoranu, Wolf Mueller, Martin Mynarek, Paul A. Northcott, Kristian W. Pajtler, Werner Paulus, Arie Perry, Ingmar Blümcke, Karl H. Plate, Michael Platten, Matthias Preusser, Torsten Pietsch, Marco Prinz, Guido Reifenberger, Bjarne W. Kristensen, Marcel Kool, Volker Hovestadt, David Ellison, Thomas Jacques, Pascale Varlet, Nima Etminan, Michael Weller, Christine White, Olaf Witt, Christel Herold-Mende, Jürgen Debus, Sandro M. Krieg, Wolfgang Wick, Matija Snuderl, Sebastian Brandner, Cynthia Hawkins, Craig M Horbinski, Christian Thomas, Pieter Wesseling, Andreas von Deimling, David Capper, Stefan M. Pfister, Felix Sahm, Florian Selt, Rolf Buslei, Volkmar Hans, Stephan Tippelt, Ralf Ketter, Patricia Kohlhof, Ken Aldape
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Cell Press
Verified
Author Correction: A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas - Nature Communications
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Correction to: Nature Communications https://doi.org/10.1038/s41467-025-61820-z, published online 31 July 2025 In the version of the article initially published, there were errors in the ninth paragraph of the Results, where in the text now reading “Within the DFCI and KiTZ cohorts, in which all tumors underwent review by a pediatric neuropathologist, 85% (17/20) of all FGFR1 rearrangements and/or ITDs occurred in the context of pLGGs, versus 15% (3/20) in the pHGGs,” 85% (17/20) was...
By April Apfelbaum, Dominik Sturm, Georges Ayoub, Bhavyaa Chandarana, Dana Novikov, Tania Jones, Jared Collins, Kelly Cai, Hyesung Jeon, Jinhua Wang, Patrick Rechter, Karthikeyan Murugesan, Meagan Montesion, Lee A. Albacker, Philipp Sievers, Felix Sahm, Kee Kiat Yeo, Tom Rosenberg, Susan N. Chi, Steven Hebert, Alberto Picca, Valérie Larouche, Sara J. Buhrlage, Mehdi Touat, Nada Jabado, Eric S. Fischer, Olaf Witt, Claudia L. Kleinman, Denise Sheer, Keith L. Ligon
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Nature
Verified
A spatial map of MAPK-activated immunosuppressive myeloid populations in pediatric low-grade glioma - Nature Immunology
Abstract Pediatric low-grade gliomas (pLGGs) are mitogen-activated protein kinase (MAPK) pathway-activated brain tumors prevalent in children and are associated with morbidity despite favorable survival. Here using imaging mass cytometry, we spatially characterized at the single-cell level the tumor microenvironment (TME) of 120 pLGG cases, considering age, molecular drivers, brain location and tumor subtype.
A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas - Nature Communications
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Abstract Oncogenic alterations in fibroblast growth factor receptor (FGFR)-family proteins occur across cancers, including pediatric gliomas. Our genomic analysis of 11,635 gliomas across ages finds that 5.3% of all gliomas harbor FGFR alterations, with an incidence of almost 9% in pediatric gliomas. Alterations in FGFR proteins are differentially enriched by age, tumor grade, and histology, with FGFR1 alterations associated with glioneuronal histologies.
By April Apfelbaum, Dominik Sturm, Georges Ayoub, Bhavyaa Chandarana, Tania Jones, Jared Collins, Kelly Cai, Hyesung Jeon, Jinhua Wang, Karthikeyan Murugesan, Meagan Montesion, Lee A. Albacker, Philipp Sievers, Felix Sahm, Kee Kiat Yeo, Tom Rosenberg, Susan N. Chi, Steven Hebert, Alberto Picca, Valérie Larouche, Sara J. Buhrlage, Mehdi Touat, Nada Jabado, Eric S. Fischer, Olaf Witt, Claudia L. Kleinman, Keith L. Ligon, Dana Novikov, Patrick Rechter, Denise Sheer
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Nature
Verified
Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics - Nature Cancer
Abstract The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility.
Soft Tissue Undifferentiated Sarcoma Carrying a Novel Onecut1::Nutm1 Fusion
Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request.
A comprehensive histomolecular characterization of meningioangiomatosis: Further evidence for a precursor neoplastic lesion
1 INTRODUCTION Meningioangiomatosis (MAM) is a poorly studied, rare, benign, and epileptogenic brain meningovascular lesion. Only about 200 cases have been reported to date [1, 2]. The majority of MAM are sporadic, affecting predominantly male patients, younger than 20 years of age [3]. Epileptic seizures constitute the main symptom and represent a clinical concern with more than 80% of patients having uncontrolled seizures at the time of surgery [3]. Surgery is the first-line treatment.
Reverse Engineering of Radical Polymerizations by Multi-Objective Optimization
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1 - Nature Communications
Abstract Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved.
Reverse Engineering of Radical Polymerizations by Multi-objective Optimization
Preprint Article Version 1 This version is not peer-reviewed Version 1 : Received: 2 February 2024 / Approved: 4 February 2024 / Online: 5 February 2024 (07:10:26 CET) Fiosina, J.; Sievers, P.; Kanagaraj, G.; Drache, M.; Beuermann, S. Reverse Engineering of Radical Polymerizations by Multi-objective Optimization. Preprints 2024, 2024020199. https://doi.org/10.20944/preprints202402.0199.v1 Fiosina, J.; Sievers, P.; Kanagaraj, G.; Drache, M.; Beuermann, S.
Author Correction: Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology - Nature Medicine
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Correction to: Nature Medicine https://doi.org/10.1038/s41591-023-02255-1. Published online 16 March 2023. In the version of this article initially published, Arend Koch (Department of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin, Germany), Martin U. Schuhmann (Department of Neurosurgery, University of Tuebingen, Tuebingen, Germany) and Ulrich W.
By Dominik Sturm, David Capper, Felipe Andreiuolo, Christian Kölsche, Philipp Sievers, Annika K Wefers, Azadeh Ebrahimi, Gerrit H. Gielen, Bjarne Daenekas, Ulrich Schüller, Christine White, Elizabeth M. Algar, Jordan Hansford, Nicholas G Gottardo, Pablo Hernáiz Driever, Astrid K. Gnekow, Hermann L. Müller, Gudrun Fleischhack, Uwe Kordes, Martin Mynarek, Michael C. Frühwald, Christof M. Kramm, Andreas von Deimling
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Nature
Verified
Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature - npj Precision Oncology
Abstract Pediatric neoplasms in the central nervous system (CNS) show extensive clinical and molecular heterogeneity and are fundamentally different from those occurring in adults. Molecular genetic testing contributes to accurate diagnosis and enables an optimal clinical management of affected children.
Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology - Nature Medicine
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Abstract The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology.
By Dominik Sturm, David Capper, Felipe Andreiuolo, Philipp Sievers, Annika K Wefers, Ulrich Schüller, Christine White, Jordan Hansford, Nicholas G Gottardo, Pablo Hernáiz Driever, Astrid K. Gnekow, Hermann L. Müller, Gudrun Fleischhack, Uwe Kordes, Martin Mynarek, Christof M. Kramm, Andreas von Deimling, Christian Kölsche, Azadeh Ebrahimi, Gerrit H. Gielen, Bjarne Daenekas, Elizabeth M. Algar, Michael C. Frühwald
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Nature
Verified
Autonomous rhythmic activity in glioma networks drives brain tumour growth - Nature
Abstract Diffuse gliomas, particularly glioblastomas, are incurable brain tumours1. They are characterized by networks of interconnected brain tumour cells that communicate via Ca2+ transients2,3,4,5,6. However, the networks’ architecture and communication strategy and how these influence tumour biology remain unknown.
Clinical implementation of integrated molecular‐morphologic risk prediction for meningioma
1 INTRODUCTION Meningiomas are the most common intracranial tumors in adult patients [1]. Historically, the diagnosis and grading of meningiomas relied on histological examination. As for other central nervous system (CNS) tumors, molecular markers have gradually been introduced for the risk prediction of meningiomas [2].
Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2 mutant meningiomas in mice
Frank Szulzewsky1, Sonali Arora1, Aleena K.S. Arakaki1, Philipp Sievers2,3, Damian A. Almiron Bonnin1, Patrick J. Paddison1,4, Felix Sahm2,3,5, Patrick J. Cimino1,6, Taranjit S. Gujral1,4 and Eric C.
Integrated Molecular-Morphologic Meningioma Classification: A Multicenter Retrospective Analysis, Retrospectively and Prospectively Validated
Molecular markers have amended or replaced histologic classification and grading criteria for many brain tumor types. For meningioma, TERT promoter mutation or homozygous deletion of CDKN2A/B is included in the 2021 WHO classification as independent criteria of WHO grade 3 meningioma.1-3 CONTEXT Key Objective The WHO classification of meningiomas stratifies patient cohorts into three groups with low to high risk of progression.
Accurate calling of KIAA1549‐BRAF fusions from DNA of human brain tumours using methylation array‐based copy number and gene panel sequencing data
ORIGINAL ARTICLE Damian Stichel Corresponding Author damian.stichel@med.uni-heidelberg.de Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Correspondence Damian Stichel, Department of Neuropathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
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