脊髓性肌萎缩症是一种常染色体隐性遗传疾病，如果不进行治疗，会导致运动神经元退化和进展性的生命贬值性运动障碍。Onasemnogene abeparvovec是一种基于九型腺病毒相关病毒的基因治疗，可以改善症状明显和无症状患者的生存率、运动功能和运动里程碑的达成。尽管腺病毒相关病毒基因组在细胞中以环状DNA的方式存在，但基因组插入可能存在潜在的致瘤风险。我们报告了一个16个月大的男婴，他在接受Onasemnogene abeparvovec治疗大约14个月后被诊断出脊髓性肌萎缩症的上皮样肿瘤。原位杂交分析发现Onasemnogene abeparvovec核酸信号广泛分布在许多但不是所有的肿瘤细胞中。对患者的形态固定石蜡包埋肿瘤样本进行整合位点分析未能检测到Onasemnogene abeparvovec的高置信度整合位点。这一发现被认为不确定，原因是剩余组织/ DNA样品有限。创新的脊髓性肌萎缩症疗法，包括Onasemnogene abeparvovec，提高了患者预期寿命，为分析这些疗法的长期不良事件和持久性提供了机会，同时也有帮助发现之前因这些患者过早死亡而未被认识到的潜在疾病相关性。版权所有©2023作者。由Elsevier Inc.出版。保留所有权利。

Spinal muscular atrophy is an autosomal recessive disease resulting in motor neuron degeneration and progressive life-limiting motor deficits if untreated. Onasemnogene abeparvovec is an adeno-associated virus serotype 9-based gene therapy that improves survival, motor function, and motor milestone achievement in symptomatic and presymptomatic patients. Although the adeno-associated virus genome is maintained as an episome, theoretical risk of tumorigenicity persists should genomic insertion occur. We present the case of a 16-month-old male with spinal muscular atrophy who was diagnosed with an epithelioid neoplasm of the spinal cord approximately 14 months after receiving onasemnogene abeparvovec. In situ hybridization analysis detected onasemnogene abeparvovec nucleic acid signal broadly distributed in many but not all tumor cells. Integration site analysis on patient formalin-fixed paraffin-embedded tumor samples failed to detect high confidence integration sites of onasemnogene abeparvovec. The finding was considered inconclusive because of limited remaining tissue/DNA input. The improved life expectancy resulting from innovative spinal muscular atrophy therapies, including onasemnogene abeparvovec, has created an opportunity to analyze the long-term adverse events and durability of these therapies as well as identify potential disease associations that were previously unrecognized because of the premature death of these patients.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.