Institute of Oncology, Department of Basic Oncology, Dokuz Eylül University, Izmir, Turkey.
Institute of Oncology, Department of Clinical Oncology, Dokuz Eylül University, Izmir, Turkey.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231211138. doi: 10.1177/15330338231211138.
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.
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.
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 ( = .028). R1275Q and F1174-related mutations were predominant; I1171T, L1226F, S1189F, V1135A, and G1125S mutations were rare. Duplicate samples did not exhibit any heterogeneity.
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.
在神经母细胞瘤中，间变性淋巴瘤激酶突变最近作为神经母细胞瘤治疗的分子靶点引起了关注，因为 6%至 10%的神经母细胞瘤患者存在间变性淋巴瘤激酶突变。土耳其的病例数据很少。我们旨在使用下一代测序检测神经母细胞瘤中的间变性淋巴瘤激酶突变和分子异质性。这是土耳其首例此类研究。
使用 Illumina MiniSeq 定制基因面板进行下一代测序分析。选择有临床意义的突变进行分析。我们还从土耳其儿科肿瘤学组收集了患者的临床数据，将其与间变性淋巴瘤激酶突变相关联。本研究为回顾性横断面研究。我们在本研究中遵循 STROBE 指南（https://www.equator-network.org/reporting-guidelines/strobe/）。
我们分析了 108 例神经母细胞瘤患者的间变性淋巴瘤激酶，平均年龄为 43.76 个月。在 13 例患者（12.04%）中检测到致病性间变性淋巴瘤激酶突变。我们注意到，间变性淋巴瘤激酶突变主要发生在中高危患者中（=0.028）。R1275Q 和 F1174 相关突变为主；I1171T、L1226F、S1189F、V1135A 和 G1125S 突变罕见。重复样本未显示任何异质性。
我们发现 F1174 和 R1275Q 相关的间变性淋巴瘤激酶突变是神经母细胞瘤中最常见的致病性突变。间变性淋巴瘤激酶突变状态未显示任何异质性，且突变与中高危组相关。
