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@ARTICLE{Rosswog:271246,
author = {C. Rosswog and J. Fassunke and A. Ernst and B.
Schömig-Markiefka and S. Merkelbach-Bruse and C.
Bartenhagen and M. Cartolano and S. Ackermann and J.
Theissen and M. Blattner-Johnson$^*$ and B. Jones$^*$ and K.
Schramm$^*$ and J. Altmüller and P. Nürnberg and M.
Ortmann and F. Berthold and M. Peifer and R. Büttner and F.
Westermann and J. H. Schulte and T. Simon and B. Hero and M.
Fischer},
title = {{G}enomic {ALK} alterations in primary and relapsed
neuroblastoma.},
journal = {British journal of cancer},
volume = {128},
number = {8},
issn = {0007-0920},
address = {Edinburgh},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2023-00378},
pages = {1559-1571},
year = {2023},
note = {2023 Apr;128(8):1559-1571},
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.},
cin = {B360 / HD01},
ddc = {610},
cid = {I:(DE-He78)B360-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36807339},
doi = {10.1038/s41416-023-02208-y},
url = {https://inrepo02.dkfz.de/record/271246},
}