文章：

初诊为非高危神经母细胞瘤中与高危险度临床病程相关的分子特征

Molecular Features Associated with a High-Risk Clinical Course in Neuroblastomas Initially Diagnosed as Non-High-Risk

原文发布日期：12 January 2026

DOI: 10.3390/cancers18020235

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Some patients initially diagnosed with non-high-risk neuroblastoma follow a high-risk clinical course and have poor survival compared to those initially diagnosed with high-risk neuroblastoma. We aimed to identify molecular aberrations present at diagnosis that may explain the high-risk clinical course in this patient group.Methods: Data were collected from non-high-risk neuroblastoma patients diagnosed at our center between 2014 and 2021. Segmental chromosomal aberrations (SCAs), gene amplifications and mutations at diagnosis were detected by a single-nucleotide polymorphism array and next-generation sequencing. Telomere maintenance mechanisms (TMMs) were investigated using fluorescent in situ hybridization, whole genome sequencing (WGS) and RNA sequencing. SCA counts were imputed by using multiple imputation.Results: The total cohort included 89 patients. Thirteen patients developed a high-risk clinical course (group A) due to progression (n = 4), local relapse (n = 4), refractory disease (n = 3) or metastases (n = 2). Seventy-six patients followed a non-high-risk clinical course (group B). An SCA profile (≥1 SCA) was present in 76% of patients in group A and only 15% in group B (p= 0.004). 1p deletion was associated with a high-risk clinical course (p= 0.034). Gains of 1q, 2p and 17q, and deletions of 4p and 11q were more common in group A. After imputation, SCA count was associated with a high-risk clinical course (pooled OR 1.256 with 95% CI 1.006–1.568,p= 0.044). Two patients, both group A, exhibitedMDM2/CDK4amplification. Alternative lengthening of telomeres (ALT) was activated in 57% of group A.Conclusions: SCA profile and 1p deletion are associated with a high-risk clinical course. ALT activation,MDM2/CDK4co-amplification, SCA count, gains of 1q, 2p, and 17q, and deletions of 4p and 11q may also be relevant molecular markers. Larger studies are needed for confirmation of these findings.

摘要翻译： 

背景/目的：一些最初被诊断为非高风险神经母细胞瘤的患者，其临床病程却呈现高风险特征，与最初诊断为高风险神经母细胞瘤的患者相比生存率较差。我们旨在识别诊断时存在的分子异常，以解释该患者群体的高风险临床病程。

方法：数据收集自2014年至2021年间在我中心诊断的非高风险神经母细胞瘤患者。通过单核苷酸多态性阵列和下一代测序检测诊断时的节段性染色体畸变（SCAs）、基因扩增和突变。使用荧光原位杂交、全基因组测序（WGS）和RNA测序研究端粒维持机制（TMMs）。SCA计数通过多重插补法进行估算。

结果：总队列包括89名患者。十三名患者发展为高风险临床病程（A组），原因包括进展（n=4）、局部复发（n=4）、难治性疾病（n=3）或转移（n=2）。七十六名患者遵循非高风险临床病程（B组）。SCA谱（≥1个SCA）存在于A组76%的患者中，而B组仅有15%（p=0.004）。1p缺失与高风险临床病程相关（p=0.034）。1q、2p和17q的增益，以及4p和11q的缺失在A组中更常见。估算后，SCA计数与高风险临床病程相关（汇总OR 1.256，95% CI 1.006–1.568，p=0.044）。两名患者（均属A组）表现出MDM2/CDK4共扩增。端粒替代延长（ALT）在A组中57%的患者中被激活。

结论：SCA谱和1p缺失与高风险临床病程相关。ALT激活、MDM2/CDK4共扩增、SCA计数、1q、2p和17q的增益以及4p和11q的缺失也可能成为相关的分子标志物。需要更大规模的研究来证实这些发现。

原文链接：

Molecular Features Associated with a High-Risk Clinical Course in Neuroblastomas Initially Diagnosed as Non-High-Risk