Journal Article

DKFZ-2023-00550

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology.

Sturm, D. (First author)DKFZ* ; Capper, D.DKFZ* ; Andreiuolo, F. ; Gessi, M. ; Kölsche, C. ; Reinhardt, A. ; Sievers, P. ; Wefers, A. K. ; Ebrahimi, A.DKFZ* ; Suwala, A. K.DKFZ* ; Gielen, G. H. ; Sill, M.DKFZ* ; Schrimpf, D. ; Stichel, D.DKFZ* ; Hovestadt, V. ; Daenekas, B. ; Rode, A.DKFZ* ; Hamelmann, S.DKFZ* ; Previti, C.DKFZ* ; Jäger, N.DKFZ* ; Buchhalter, I.DKFZ* ; Blattner-Johnson, M.DKFZ* ; Jones, B. C.DKFZ* ; Warmuth-Metz, M. ; Bison, B. ; Grund, K. ; Sutter, C. ; Hirsch, S.DKFZ* ; Dikow, N. ; Hasselblatt, M. ; Schüller, U. ; Gerber, N. U. ; White, C. L. ; Buntine, M. K. ; Kinross, K. ; Algar, E. M. ; Hansford, J. R. ; Gottardo, N. G. ; Hernáiz Driever, P. ; Gnekow, A. ; Witt, O.DKFZ* ; Müller, H. L. ; Calaminus, G. ; Fleischhack, G. ; Kordes, U. ; Mynarek, M. ; Rutkowski, S. ; Frühwald, M. C. ; Kramm, C. M. ; von Deimling, A.DKFZ* ; Pietsch, T. ; Sahm, F. (Last author)DKFZ* ; Pfister, S. M. (Last author)DKFZ* ; Jones, D. (Last author)DKFZ*

2023
Nature America Inc. New York, NY

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Please use a persistent id in citations: doi:10.1038/s41591-023-02255-1

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. 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.

Note: #EA:B360#LA:B300#LA:B062#LA:B360# / 2023 Apr;29(4):917-926

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Contributing Institute(s):

1. Pädiatische Gliomforschung (B360)
2. DKTK Koordinierungsstelle Berlin (BE01)
3. KKE Neuropathologie (B300)
4. B062 Pädiatrische Neuroonkologie (B062)
5. W610 Core Facility Omics IT (W610)
6. KKE Pädiatrische Onkologie (B310)
7. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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