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Identification of ALK Mutation in Neuroblastoma on the Point of Molecular Heterogeneity
Tekincan Çağrı Aktaş1, Deniz Kızmazoğlu2, Safiye Aktaş1
1Institute of Oncology, Department of Basic Oncology, Dokuz Eylül University, Izmir, Turkey.
Background And Aim:
In neuroblastoma, anaplastic lymphoma kinase mutations have recently received attention as molecular targets for the treatment of neuroblastoma, as 6% to 10% of patients with neuroblastoma have anaplastic lymphoma kinase mutations. There are little data from the cases in Turkey. We aimed to detect anaplastic lymphoma kinase mutations and molecular heterogeneity in neuroblastoma using next-generation sequencing. This study is the first one with this many cases in Turkey.
Methods:
Next-generation sequencing analysis was performed using an Illumina MiniSeq custom gene panel. Clinically important mutations were selected for the analysis. We also gathered clinical data of the patients from Turkish Pediatric Oncology Group cohorts to associate them with anaplastic lymphoma kinase mutations. This study is a retrospective cross-sectional study. We followed STROBE guideline (https://www.equator-network.org/reporting-guidelines/strobe/) on this study.
Results:
We analyzed anaplastic lymphoma kinase in 108 patients with neuroblastoma, with a mean age of 43.76 months. Pathogenic anaplastic lymphoma kinase mutations were detected in 13 patients (12.04%). We noted that anaplastic lymphoma kinase mutations were primarily observed in intermediate- and high-risk patients (P = .028). R1275Q and F1174-related mutations were predominant; I1171T, L1226F, S1189F, V1135A, and G1125S mutations were rare. Duplicate samples did not exhibit any heterogeneity.
Conclusions:
We found that F1174 and R1275Q-related anaplastic lymphoma kinase mutations are the most common pathogenic mutations in neuroblastoma. Anaplastic lymphoma kinase mutation status did not show any heterogeneity, and the mutations were correlated with intermediate- or high-risk groups.
Insights
Anaplastic lymphoma kinase (ALK) mutations were found in 12.04% of Turkish neuroblastoma patients, predominantly in high-risk groups. No molecular heterogeneity was observed, suggesting ALK as a potential therapeutic target.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Anaplastic lymphoma kinase (ALK) mutations are emerging molecular targets in neuroblastoma treatment.
- Approximately 6-10% of neuroblastoma patients harbor ALK mutations, but data from Turkey is limited.
- This study addresses the gap in understanding ALK mutations in the Turkish neuroblastoma population.
Purpose of the Study:
- To detect anaplastic lymphoma kinase (ALK) mutations in Turkish neuroblastoma patients.
- To investigate molecular heterogeneity associated with ALK mutations.
- To correlate ALK mutation status with clinical risk groups.
Main Methods:
- Next-generation sequencing (NGS) using a custom gene panel on 108 neuroblastoma patients.
- Analysis of clinically significant mutations, including ALK.
- Retrospective cross-sectional study adhering to STROBE guidelines, correlating with Turkish Pediatric Oncology Group data.
Main Results:
- Pathogenic anaplastic lymphoma kinase (ALK) mutations were identified in 13 out of 108 patients (12.04%).
- Mutations were significantly more prevalent in intermediate- and high-risk neuroblastoma patients (P=.028).
- F1174 and R1275Q-related mutations were predominant; no heterogeneity was observed in duplicate samples.
Conclusions:
- F1174 and R1275Q are the most common pathogenic anaplastic lymphoma kinase (ALK) mutations in this Turkish cohort.
- ALK mutation status in neuroblastoma did not exhibit heterogeneity.
- ALK mutations are correlated with intermediate- and high-risk neuroblastoma classifications.
