癌症杂志刊登的一项研究显示，神经母细胞瘤中常见重复发生靶向酪氨酸激酶（ALK）基因的基因组突变。然而，它们的时间演变信息仍然很少。研究人员在诊断和/或复发时评估了ALK突变体在943名神经母细胞瘤患者中的频率，涵盖了该疾病的所有阶段。对个别患者的疾病样本进行长期信息进行了评估。在101例和102例样本中分别获得了突变和扩增状态的纵向信息。在诊断时，ALK点突变在所有病例中发生的概率为10.5％，在<18个月的第4阶段患者中频率最高。在复发时，ALK基因突变的频率增加了70％，在高风险和非高风险病例中都有所增加。增加最有可能是由于初发突变，经常导致R1275Q置换，这对药物治疗敏感。相比之下，ALK扩增的频率在疾病过程中没有变化。ALK扩增与患者不良预后有关，但突变没有。复发时ALK突变的极大增加以及它们在年轻第4阶段患者中的高发生率表明，应该定期调查这些患者队列中的基因组ALK状态，并在中度风险患者中评估ALK靶向治疗。 ©2023年作者。

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.© 2023. The Author(s).