Journal Article

DKFZ-2025-02160

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Harmonization of reporting for detection of ALK genetic alterations in neuroblastoma - a SIOPEN Biology study.

Saint-Charles, A. ; Masliah-Planchon, J. ; Saberi-Ansari, E. ; Bellini, A. ; Bernkopf, M. ; Font de Mora, J. ; Salvá, R. N. ; Van Roy, N. ; Goodman, A. ; Vicha, A. ; Attignon, V. ; Combaret, V. ; Beiske, K. ; Martinsson, T. ; Schoumans, J. ; Rossing, M. ; Tops, B. ; Westermann, F.DKFZ* ; Cotteret, S. ; Fischer, M. ; Birger, Y. ; Mazzocco, K. ; Chesler, L. ; Betts, D. ; Cowley, M. ; Capasso, M. ; Bobin, C. ; Iddir, Y. ; Zaidi, S. ; Carcaboso, A. M. ; Vandermeulen, J. ; Loontiens, S. ; Gaarder, J. ; Ibrahim, R. R. ; Rosswog, C. ; Hameiri-Grossman, M. ; Shichrur, K. ; Trahair, T. ; Barahona, P. ; Eggert, A.DKFZ* ; Deubzer, H. E.DKFZ* ; Delattre, O. ; Pasqualini, C. ; George, S. ; Tytgat, G. ; Tweddle, D. A. ; Taschner-Mandl, S. ; Schleiermacher, G.

2025
Elsevier Amsterdam [u.a.]

Abstract: In high-risk neuroblastoma, identification of ALK activating genetic alterations is considered for clinical decision-making in relapse or more recently frontline treatment. The accurate diagnosis of genetic alterations requires harmonization of molecular techniques and reporting especially when these are considered as inclusion criteria for clinical trials. Analysis and validation was preformed across the 21 SIOPEN (International Society of Paediatric Oncology Europe Neuroblastoma) molecular diagnostic laboratories, with 14 DNA samples harbouring distinct ALK alterations including ALK mutations in or outside hotspots in the tyrosine kinase domain (TKD) with variant allele frequencies (VAF) ranging from 1% to 91%, or ALK genomic amplification shared between the laboratories. Each laboratories employed their own established techniques: ALK amplifications were detected using either pan-genomic copy number techniques or fluorescence in situ hybridization and ALK mutations were characterized by Next Generation Sequencing (NGS) techniques. All laboratories correctly identified high-level ALK amplification and ALK mutations within the TKD hotspots with VAF >5%, with exception of 2 cases. Difference in interpretation and reporting was apparent for samples harbouring mutations with a VAF <5% or outside known hotspots. These results highlight the importance of standard operating procedures, standardized reporting, and the robustness of ALK genetic testing in the SIOPEN laboratories, as well as the need for expert discussions on atypical ALK alterations, to validate eligibility for ALK targeted treatment in clinical trials.

Keyword(s): ALK genetic alteration ; High-Risk neuroblastoma ; International standardization test ; Next-generation sequencing ; Reporting results

Note: epub

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Contributing Institute(s):

1. B087 Neuroblastom Genomik (B087)
2. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

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

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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