DNA methylation-based classification of sinonasal tumors.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
28 11 2022
Historique:
received: 31 03 2022
accepted: 07 11 2022
entrez: 28 11 2022
pubmed: 29 11 2022
medline: 1 12 2022
Statut: epublish

Résumé

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs.

Identifiants

pubmed: 36443295
doi: 10.1038/s41467-022-34815-3
pii: 10.1038/s41467-022-34815-3
pmc: PMC9705411
doi:

Substances chimiques

SMARCA4 protein, human EC 3.6.1.-
DNA Helicases EC 3.6.4.-
Nuclear Proteins 0
Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

7148

Informations de copyright

© 2022. The Author(s).

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Auteurs

Philipp Jurmeister (P)

Institute of Pathology, Ludwig Maximilians University Hospital Munich, Munich, Germany. philipp.jurmeister@med.uni-muenchen.de.
Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. philipp.jurmeister@med.uni-muenchen.de.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany. philipp.jurmeister@med.uni-muenchen.de.
German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany. philipp.jurmeister@med.uni-muenchen.de.

Stefanie Glöß (S)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

Renée Roller (R)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Proteomics Platform, Berlin Institute of Health (BIH) and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.

Maximilian Leitheiser (M)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Simone Schmid (S)

German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

Liliana H Mochmann (LH)

Institute of Pathology, Ludwig Maximilians University Hospital Munich, Munich, Germany.

Emma Payá Capilla (E)

Institute of Pathology, Ludwig Maximilians University Hospital Munich, Munich, Germany.

Rebecca Fritz (R)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Carsten Dittmayer (C)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

Corinna Friedrich (C)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
MDC Graduate School, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Humboldt Universität zu Berlin, Institute of Chemistry, Berlin, Germany.

Anne Thieme (A)

German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

Philipp Keyl (P)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Armin Jarosch (A)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Simon Schallenberg (S)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Hendrik Bläker (H)

Institute of Pathology, University Hospital Leipzig, Leipzig, Germany.

Inga Hoffmann (I)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Claudia Vollbrecht (C)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Annika Lehmann (A)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Michael Hummel (M)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Daniel Heim (D)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Mohamed Haji (M)

Proteomics Platform, Berlin Institute of Health (BIH) and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.

Patrick Harter (P)

German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Neurology (Edinger Institute), Goethe-University Frankfurt am Main, Frankfurt am Main, Germany.
German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Benjamin Englert (B)

Institute of Neuropathology, Ludwig Maximilians University Hospital Munich, Munich, Germany.

Stephan Frank (S)

Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Jürgen Hench (J)

Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Werner Paulus (W)

Institute of Neuropathology, University Hospital Münster, Münster, Germany.

Martin Hasselblatt (M)

Institute of Neuropathology, University Hospital Münster, Münster, Germany.

Wolfgang Hartmann (W)

Division of Translational Pathology, Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Münster, Germany.

Hildegard Dohmen (H)

Institute of Neuropathology, University of Giessen, Giessen, Germany.

Ursula Keber (U)

Institute of Neuropathology, Philipps-University, Marburg, Germany.

Paul Jank (P)

Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg, Germany.

Carsten Denkert (C)

Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg, Germany.

Christine Stadelmann (C)

Institute for Neuropathology, University Medical Centre Göttingen, Göttingen, Germany.

Felix Bremmer (F)

Institute of Pathology, University Medical Center, Göttingen, Germany.

Annika Richter (A)

Institute of Pathology, University Medical Center, Göttingen, Germany.

Annika Wefers (A)

Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Julika Ribbat-Idel (J)

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

Sven Perner (S)

Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
German Center for Lung Research (DZL), Partner Site Luebeck, Luebeck, Germany.

Christian Idel (C)

Department of Otorhinolaryngology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.

Lorenzo Chiariotti (L)

Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131, Naples, Italy.
CEINGE Biotecnologie Avanzate, 80145, Naples, Italy.

Rosa Della Monica (R)

CEINGE Biotecnologie Avanzate, 80145, Naples, Italy.

Alfredo Marinelli (A)

Department of Medicina Clinica e Chirurgia, University Federico II, Naples, Italy.

Ulrich Schüller (U)

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.

Michael Bockmayr (M)

Institute of Pathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.

Jacklyn Liu (J)

UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.
UCL Academic Head and Neck Centre, Division of Surgery and Interventional Science, University College London, London, UK.

Valerie J Lund (VJ)

UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.
UCL Academic Head and Neck Centre, Division of Surgery and Interventional Science, University College London, London, UK.

Martin Forster (M)

UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.
UCL Academic Head and Neck Centre, Division of Surgery and Interventional Science, University College London, London, UK.

Matt Lechner (M)

UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.
UCL Academic Head and Neck Centre, Division of Surgery and Interventional Science, University College London, London, UK.

Sara L Lorenzo-Guerra (SL)

Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.

Mario Hermsen (M)

Department of Head and Neck Oncology, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.

Pascal D Johann (PD)

Swabian Childrens' Cancer Center, University Childrens' Hospital Augsburg and EU-RHAB Registry, Augsburg, Germany.

Abbas Agaimy (A)

Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany.

Philipp Seegerer (P)

Machine-Learning Group, Department of Software Engineering and Theoretical Computer Science, Technical University of Berlin, Berlin, Germany.

Arend Koch (A)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

Frank Heppner (F)

German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

Stefan M Pfister (SM)

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 Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.

David T W Jones (DTW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Martin Sill (M)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Andreas von Deimling (A)

Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Matija Snuderl (M)

Division of Neuropathology, NYU Langone Health, New York, USA.
Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, USA.
Division of Molecular Pathology and Diagnostics, NYU Langone Health, New York, USA.

Klaus-Robert Müller (KR)

Machine-Learning Group, Department of Software Engineering and Theoretical Computer Science, Technical University of Berlin, Berlin, Germany.
Department of Artificial Intelligence, Korea University, Seoul, South Korea.
Max-Planck-Institute for Informatics, Saarbrücken, Germany.
BIFOLD - Berlin Institute for the Foundations of Learning and Data, Berlin, Germany.

Erna Forgó (E)

Stanford University School of Medicine, Stanford, CA, USA.

Brooke E Howitt (BE)

Stanford University School of Medicine, Stanford, CA, USA.

Philipp Mertins (P)

Proteomics Platform, Berlin Institute of Health (BIH) and Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany.

Frederick Klauschen (F)

Institute of Pathology, Ludwig Maximilians University Hospital Munich, Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
BIFOLD - Berlin Institute for the Foundations of Learning and Data, Berlin, Germany.

David Capper (D)

German Cancer Consortium (DKTK), Partner Site Berlin, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Charitéplatz 1, Berlin, Germany.

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