单核苷酸多态性(SNP)阵列分析有助于识别与神经母细胞瘤疾病相关的新型染色体改变以及与药物不良反应相关的单核苷酸多态性。

SNP array analysis facilitates the identification of novel chromosomal alterations associated with disease and SNPs related to adverse drug reactions in neuroblastoma.

作者信息

Chen Kailan, Li Hanpeng, Luo Yujie, Liu Jiaqi, Liu Huichao, Tian Yongli, Yu Yifei, Xu Yun, Chen Li, Xu Qiong, Li Ying

机构信息

Department of Oncology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430016, P.R. China.

Department of Medicine, Shanghai Cinopath Medical Laboratory Co., Ltd., Shanghai 200120, P.R. China.

出版信息

Oncol Lett. 2025 Mar 24;29(5):242. doi: 10.3892/ol.2025.14988. eCollection 2025 May.

Abstract

Chromosomal abnormalities are common characteristics of neuroblastoma, and have been associated with treatment, relapse and survival risk factors. The processes governing the incidence or advancement of chromosomal copy number abnormalities remain unclear, despite progress in understanding their prognostic implications. The present study aimed to provide a comprehensive understanding of genetic alterations, clinical implications, and the association between copy number aberrations (CNAs) and clinical parameters. Single nucleotide polymorphism (SNP) array analysis was performed on a set of 45 neuroblastoma samples to examine chromosomal CNAs and SNPs. Logistic regression analysis was performed to identify SNPs associated with adverse drug reactions (ADRs). In the present study, numerous CNAs were observed in 92% of neuroblastoma tumors, while CNAs were found in 15% of ganglioneuroblastoma tumors. The segmental alterations were mainly observed in stage 3 or 4 neuroblastoma cases that had tumor sizes >10 cm. The present study concentrated on analyzing entire chromosome modifications and revealed that, in contrast to gain, loss of heterozygosity (LOH) mostly occurred during stages 3 and 4 of neuroblastoma. Only stage 3 and 4 neuroblastomas with tumor sizes >10 cm were found to exhibit loss of the Y chromosome, which was associated with similar clinical characteristics as segmental alterations. LOH of the whole chromosome might be a subgroup of whole chromosome alterations, and could be a novel prognosis and treatment marker. Using a regression model, 13 SNPs were identified to be strongly associated with ADRs following chemotherapy for neuroblastoma. Although validation studies in independent cohorts are required, the present findings support the use of CNAs and SNPs for predicting neuroblastoma treatment outcomes.

摘要

染色体异常是神经母细胞瘤的常见特征,并与治疗、复发及生存风险因素相关。尽管在理解其预后意义方面取得了进展,但控制染色体拷贝数异常发生或进展的过程仍不清楚。本研究旨在全面了解基因改变、临床意义以及拷贝数畸变(CNA)与临床参数之间的关联。对一组45例神经母细胞瘤样本进行单核苷酸多态性(SNP)阵列分析,以检测染色体CNA和SNP。进行逻辑回归分析以鉴定与药物不良反应(ADR)相关的SNP。在本研究中,92%的神经母细胞瘤肿瘤中观察到大量CNA,而在15%的神经节神经母细胞瘤肿瘤中发现了CNA。节段性改变主要见于肿瘤大小>10 cm的3期或4期神经母细胞瘤病例。本研究集中分析整个染色体修饰,并发现与增益相反,杂合性缺失(LOH)大多发生在神经母细胞瘤的3期和4期。仅发现肿瘤大小>10 cm的3期和4期神经母细胞瘤表现出Y染色体缺失,其与节段性改变具有相似的临床特征。整条染色体的LOH可能是整条染色体改变的一个亚组,并且可能是一种新的预后和治疗标志物。使用回归模型,鉴定出13个SNP与神经母细胞瘤化疗后的ADR密切相关。尽管需要在独立队列中进行验证研究,但本研究结果支持使用CNA和SNP来预测神经母细胞瘤的治疗结果。

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