Akademik Veri Yönetim Sistemi
FRONTIERS IN BIOSCIENCE - SCHOLAR, cilt.2, sa.2, ss.1-8, 2025 (Scopus)
Background: Neuroblastoma (NB) is the most common extracranial solid tumor among pediatric cancers and
accounts for 15% of childhood cancer deaths. Neurotrophic receptor tyrosine kinases (NTRKs) are genes that play
critical roles in the development and function of the nervous system. The role of NTRKs in NB is important both
for elucidating basic biological mechanisms and for developing therapeutic approaches. NTRK fusions are being
evaluated as potential biomarkers and therapeutic targets for targeted therapy strategies. The tumor-agnostic TRK
inhibitors larotrectinib and entrectinib are used in the treatment of advanced or metastatic solid tumor cancers with
NTRK gene fusions. The aim of this study was to investigate the clinical significance of NTRK1, 2, and 3 gene
point mutations, fusions, protein expression and the effectiveness of these in targeted therapy decisions of NB.
Methods: In this study, we investigated Pan-TRK expression, point mutations, and fusions in the NTRK1, 2, and 3
genes using next generation sequencing (NGS) in 173 patients diagnosed with NB using paraffin block samples.
Findings were analyzed using clinical data, MYCN amplification, and 11Q deletion in SPSS 29.0 statistical
software using Pearson correlation analysis at a p<0.05 level.
Results: In NTRK immunohistochemistry analysis, 67.9% were NTRK positive. NGS analysis revealed NTRK1
missense point mutations in 20 cases, NTRK2 in 9 cases, and NTRK3 in 9 cases. A total of 5 fusions were
observed in 4 of the 103 patients who underwent fusion analysis.
Conclusions: Due to the presence of neural tissue, NTRKs are highly positive in immunohistochemistry (IHC), so
it is not appropriate to use them as biomarkers in the study of NTRK inhibitor sensitivity and resistance, which are
agnostic drugs. The low fusion rate is consistent with the literature, and the significance of the numerous point
mutations detected as agnostic markers should be investigated. NTRK expression, fusion, and point mutation
presence are not associated with clinical parameters or survival.