Portal de investigación
Harmonization of Reporting of ALK Genetic Alterations in Neuroblastoma: A SIOPEN Biology Study.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Saint-Charles A
- Masliah-Planchon J
- Saberi-Ansari E
- Bellini A
- Bernkopf M
- Noguera R
- Van Roy N
- Goodman A
- Vicha A
- Attignon V
- Combaret V
- Beiske K
- Martinsson T
- Schoumans J
- Rossing M
- Tops B
- Westermann F
- Cotteret S
- Fischer M
- Birger Y
- Mazzocco K
- Chesler L
- Betts D
- Cowley M
- Capasso M
- Bobin C
- Iddir Y
- Zaidi S
- Carcaboso AM
- Vandermeulen J
- Loontiens S
- Gaarder J
- Ibrahim RR
- Rosswog C
- Hameiri-Grossman M
- Shichrur K
- Trahair T
- Barahona P
- Eggert A
- Deubzer HE
- Delattre O
- Pasqualini C
- George S
- Tytgat G
- Tweddle DA
- Taschner-Mandl S
- Schleiermacher G
Grupos
Abstract
In high-risk neuroblastoma, identification of ALK activating genetic alterations is considered for clinical decision-making at relapse or more recently in frontline treatment. The accurate diagnosis of genetic alterations requires harmonization of molecular techniques and reporting, especially when these concern inclusion criteria for clinical trials. Analysis and validation of 14 DNA samples harboring distinct ALK alterations were performed across the 21 SIOPEN (International Society of Paediatric Oncology Europe Neuroblastoma) molecular diagnostic laboratories. These included ALK mutations at or outside hotspots in the tyrosine kinase domain with variant allele frequencies (VAFs) of 1% to 91% or ALK genomic amplification. Each laboratory used their own techniques: ALK amplifications were detected by pan-genomic copy number techniques or fluorescence in situ hybridization, and ALK mutations were characterized by next-generation sequencing techniques. All laboratories correctly identified high-level ALK amplification and ALK mutations within the known hotspots with VAF >5%, with the exception of two cases. Differences in interpretation and reporting were apparent for samples harboring 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, and the need for expert discussions regarding atypical ALK alterations, to validate eligibility for ALK targeted treatment in clinical trials.
Copyright © 2026 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Datos de la publicación
- ISSN/ISSNe:
- 1525-1578, 1943-7811
- Tipo:
- Article
- Páginas:
- 27-38
- PubMed:
- 41110766
- Enlace a otro recurso:
- www.scopus.com
- Factor de Impacto:
- 1,678 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
JOURNAL OF MOLECULAR DIAGNOSTICS ELSEVIER SCIENCE INC
Documentos
- No hay documentos
Filiaciones
Keywords
- anaplastic lymphoma kinase; genomic DNA; protein tyrosine kinase; ALK protein, human; Article; Australia; Belgium; biotechnology; childhood cancer; clinical decision making; comparative genomic hybridization; Czech Republic; Denmark; DNA content; fluorescence in situ hybridization; France; gene frequency; gene mutation; genetic modification; genetic screening; Germany; high throughput sequencing; human; Ireland; Israel; molecular diagnosis; Netherlands; neuroblastoma; Norway; single nucleotide polymorphism; standard operating procedure; Sweden; Switzerland; United Kingdom; diagnosis; gene amplification; genetics; mutation; procedures; Anaplastic Lymphoma Kinase; Gene Amplification; Gene Frequency; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; In Situ Hybridization, Fluorescence; Mutation; Neuroblastoma
Cita
Saint A,Masliah J,Saberi E,Bellini A,Bernkopf M,FONT DE MORA J,Noguera R,Van N,Goodman A,Vicha A,Attignon V,Combaret V,Beiske K,Martinsson T,Schoumans J,Rossing M,Tops B,Westermann F,Cotteret S,Fischer M,Birger Y,Mazzocco K,Chesler L,Betts D,Cowley M,Capasso M,Bobin C,Iddir Y,Zaidi S,Carcaboso AM,Vandermeulen J,Loontiens S,Gaarder J,Ibrahim RR,Rosswog C,Hameiri M,Shichrur K,Trahair T,Barahona P,Eggert A,Deubzer HE,Delattre O,Pasqualini C,George S,Tytgat G,Tweddle DA,Taschner S,Schleiermacher G. Harmonization of Reporting of ALK Genetic Alterations in Neuroblastoma: A SIOPEN Biology Study. J. Mol. Diagn. 2026. 28. (1):p. 27-38. IF:3,900. (1).