Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology.

Adolescent Humans Child Multiomics Glioma / diagnosis Neuropathology DNA Methylation / genetics Mutation Brain Neoplasms / diagnosis

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
04 2023
Historique:
received: 04 08 2022
accepted: 13 02 2023
medline: 21 4 2023
pubmed: 18 3 2023
entrez: 17 3 2023
Statut: ppublish

Résumé

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. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.

Identifiants

DOI: 10.1038/s41591-023-02255-1 PMID: 36928815 PMC: PMC10115638
pubmed: 36928815
doi: 10.1038/s41591-023-02255-1
pii: 10.1038/s41591-023-02255-1
pmc: PMC10115638
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

917-926

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

© 2023. The Author(s).

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Auteurs

Dominik Sturm (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
ORCID: 0000-0003-0250-1696

David Capper (D)

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.
ORCID: 0000-0003-1945-497X

Felipe Andreiuolo (F)

Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Laboratory of Neuropathology, Paulo Niemeyer State Brain Institute, Rio de Janeiro, Brazil.
D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
ORCID: 0000-0002-2568-6155

Marco Gessi (M)

Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.

Christian Kölsche (C)

Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
ORCID: 0000-0001-8763-8864

Annekathrin Reinhardt (A)

Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.

Philipp Sievers (P)

Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
ORCID: 0000-0003-3237-6021

Annika K Wefers (AK)

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0001-9394-8519

Azadeh Ebrahimi (A)

Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
ORCID: 0000-0001-7354-1746

Abigail K Suwala (AK)

Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Department of Neurological Surgery, Helen Diller Research Center, University of California, San Francisco, San Francisco, CA, USA.

Gerrit H Gielen (GH)

Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
ORCID: 0000-0002-2707-0290

Martin Sill (M)

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.

Daniel Schrimpf (D)

Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.

Damian Stichel (D)

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

Volker Hovestadt (V)

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Bjarne Daenekas (B)

Department of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-0237-8694

Agata Rode (A)

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

Stefan Hamelmann (S)

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

Christopher Previti (C)

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.

Natalie Jäger (N)

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.

Ivo Buchhalter (I)

Omics IT and Data Management Core Facility, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.

Mirjam Blattner-Johnson (M)

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

Barbara C Jones (BC)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Monika Warmuth-Metz (M)

Department of Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Würzburg, Germany.
Neuroradiological Reference Center for the Pediatric Brain Tumor (HIT) Studies of the German Society of Pediatric Oncology and Hematology, University Hospital Würzburg, since 2021 University Hospital Augsburg, Augsburg, Germany.

Brigitte Bison (B)

Neuroradiological Reference Center for the Pediatric Brain Tumor (HIT) Studies of the German Society of Pediatric Oncology and Hematology, University Hospital Würzburg, since 2021 University Hospital Augsburg, Augsburg, Germany.
Diagnostic and Interventional Neuroradiology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.

Kerstin Grund (K)

Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.

Christian Sutter (C)

Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.

Steffen Hirsch (S)

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.
Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.

Nicola Dikow (N)

Institute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.

Martin Hasselblatt (M)

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

Ulrich Schüller (U)

Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
ORCID: 0000-0002-8731-1121

Arend Koch (A)

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

Nicolas U Gerber (NU)

Department of Oncology, University Children's Hospital Zürich, Zürich, Switzerland.

Christine L White (CL)

Genetics and Molecular Pathology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.
Victorian Clinical Genetics Services, Parkville, VIC, Australia.
ORCID: 0000-0002-5920-0029

Molly K Buntine (MK)

Genetics and Molecular Pathology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.

Kathryn Kinross (K)

Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG), Hudson Institute of Medical Research, Clayton, VIC, Australia.

Elizabeth M Algar (EM)

Genetics and Molecular Pathology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia.
Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
ORCID: 0000-0002-9875-8092

Jordan R Hansford (JR)

Women's and Children's Hospital, South Australia Health and Medical Research Institute, South Australia immunoGENomics Cancer Institute, University of Adelaide, Adelaide, SA, Australia.
ORCID: 0000-0001-7733-383X

Nicholas G Gottardo (NG)

Department of Paediatric 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.
ORCID: 0000-0002-1082-6776

Martin U Schuhmann (MU)

Department of Neurosurgery, University of Tuebingen, Tuebingen, Germany.

Ulrich W Thomale (UW)

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Pablo Hernáiz Driever (P)

German HIT-LOGGIC Registry for low-grade glioma in children and adolescents, Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
ORCID: 0000-0003-3135-3872

Astrid Gnekow (A)

Swabian Children's Cancer Center, Paediatric and Adolescent Medicine, Faculty of Medicine, University Augsburg, Augsburg, Germany.
ORCID: 0000-0002-7356-6887

Olaf Witt (O)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.

Hermann L Müller (HL)

Department of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Oldenburg, Germany.
ORCID: 0000-0003-4929-9966

Gabriele Calaminus (G)

Department of Pediatric Hematology and Oncology, University Childrens' Hospital Muenster, Muenster, Germany.

Gudrun Fleischhack (G)

Pediatric Hematology and Oncology, Pediatrics III, University Children's Hospital of Essen, Essen, Germany.
ORCID: 0000-0001-5714-007X

Uwe Kordes (U)

Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0001-6375-2320

Martin Mynarek (M)

Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0003-3302-2719

Stefan Rutkowski (S)

Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Michael C Frühwald (MC)

Swabian Children's Cancer Center, Paediatric and Adolescent Medicine, Faculty of Medicine, University Augsburg, Augsburg, Germany.
ORCID: 0000-0002-8237-1854

Christof M Kramm (CM)

Department of Child and Adolescent Health, Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
ORCID: 0000-0002-5017-926X

Andreas von Deimling (A)

Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
ORCID: 0000-0002-5863-540X

Torsten Pietsch (T)

Department of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.

Felix Sahm (F)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.

Stefan M Pfister (SM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.

David T W Jones (DTW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany. david.jones@kitz-heidelberg.de.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. david.jones@kitz-heidelberg.de.
ORCID: 0000-0002-2036-5141

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Sciences de l'information › Informatique › Biologie informatique › Multi-omique › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Professions de santé › Médecine › Anatomopathologie › Neuropathologie › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Multiomic neuropathology improves diagnostic...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Multiomic neuropathology improves diagnostic...