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Genomic ALK alterations in primary and relapsed neuroblastoma

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Item Type:Article
Title:Genomic ALK alterations in primary and relapsed neuroblastoma
Creators Name:Rosswog, C. and Fassunke, J. and Ernst, A. and Schömig-Markiefka, B. and Merkelbach-Bruse, S. and Bartenhagen, C. and Cartolano, M. and Ackermann, S. and Theissen, J. and Blattner-Johnson, M. and Jones, B. and Schramm, K. and Altmüller, J. and Nürnberg, P. and Ortmann, M. and Berthold, F. and Peifer, M. and Büttner, R. and Westermann, F. and Schulte, J.H. and Simon, T. and Hero, B. and Fischer, M.
Abstract:BACKGROUND: Genomic alterations of the anaplastic lymphoma kinase gene (ALK) occur recurrently in neuroblastoma, a pediatric malignancy of the sympathetic nervous system. However, information on their development over time has remained sparse. METHODS: ALK alterations were assessed in neuroblastomas at diagnosis and/or relapse from a total of 943 patients, covering all stages of disease. Longitudinal information on diagnostic and relapsed samples from individual patients was available in 101 and 102 cases for mutation and amplification status, respectively. RESULTS: At diagnosis, ALK point mutations occurred in 10.5% of all cases, with highest frequencies in stage 4 patients <18 months. At relapse, ALK alteration frequency increased by 70%, both in high-risk and non-high-risk cases. The increase was most likely due to de novo mutations, frequently leading to R1275Q substitutions, which are sensitive to pharmacological ALK inhibition. By contrast, the frequency of ALK amplifications did not change over the course of the disease. ALK amplifications, but not mutations, were associated with poor patient outcome. CONCLUSIONS: The considerably increased frequency of ALK mutations at relapse and their high prevalence in young stage 4 patients suggest surveying the genomic ALK status regularly in these patient cohorts, and to evaluate ALK-targeted treatment also in intermediate-risk patients.
Keywords:Cancer Genetics, Paediatric Cancer
Source:British Journal of Cancer
Publisher:Nature Publishing Group
Page Range:1559-1571
Date:12 April 2023
Official Publication:https://doi.org/10.1038/s41416-023-02208-y
PubMed:View item in PubMed

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