Genomic ALK alterations in primary and relapsed neuroblastoma
| العنوان: | Genomic ALK alterations in primary and relapsed neuroblastoma |
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| المؤلفون: | Carolina Rosswog, Jana Fassunke, Angela Ernst, Birgid Schömig-Markiefka, Sabine Merkelbach-Bruse, Christoph Bartenhagen, Maria Cartolano, Sandra Ackermann, Jessica Theissen, Mirjam Blattner-Johnson, Barbara Jones, Kathrin Schramm, Janine Altmüller, Peter Nürnberg, Monika Ortmann, Frank Berthold, Martin Peifer, Reinhard Büttner, Frank Westermann, Johannes H. Schulte, Thorsten Simon, Barbara Hero, Matthias Fischer |
| المصدر: | British Journal of Cancer. 128:1559-1571 |
| بيانات النشر: | Springer Science and Business Media LLC, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, Oncology, Technology Platforms |
| الوصف: | 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 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c173d0692f4477ef1800bf9b6abe5964 https://doi.org/10.1038/s41416-023-02208-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c173d0692f4477ef1800bf9b6abe5964 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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