Journal Article

DKFZ-2023-00378

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genomic ALK alterations in primary and relapsed neuroblastoma.

Rosswog, C. ; Fassunke, J. ; Ernst, A. ; Schömig-Markiefka, B. ; Merkelbach-Bruse, S. ; Bartenhagen, C. ; Cartolano, M. ; Ackermann, S. ; Theissen, J. ; Blattner-Johnson, M.DKFZ* ; Jones, B.DKFZ* ; Schramm, K.DKFZ* ; Altmüller, J. ; Nürnberg, P. ; Ortmann, M. ; Berthold, F. ; Peifer, M. ; Büttner, R. ; Westermann, F. ; Schulte, J. H. ; Simon, T. ; Hero, B. ; Fischer, M.

2023
Nature Publ. Group Edinburgh

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41416-023-02208-y

Abstract: 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.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.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.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.

Note: 2023 Apr;128(8):1559-1571

---

Contributing Institute(s):

1. Pediatric Glioma (B360)
2. DKTK HD zentral (HD01)

Research Program(s):

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

Appears in the scientific report 2023

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---