横纹肌样瘤 (RT) 是一种侵袭性、罕见的肿瘤，主要影响幼儿，其特征是双等位基因 SMARCB1 基因失活。虽然大多数 SMARCB1 改变是从头获得的，但三分之一的病例表现出种系改变，定义为横纹肌样瘤易感综合征 (RTPS1)。随着下一代测序 (NGS) 灵敏度的提高，与遗传疾病相关的基因中的嵌合现象更容易被检测到。本研究的重点是使用定制的 NGS panel 探索 SMARCB1 种系改变，特别是接受 RT 的儿童和父母的血液样本中的镶嵌现象。对 280 名儿童和 140 名父母进行种系分析的队列进行了研究。使用针对 SMARCB1 基因的平均深度为 1,500 倍的定制 NGS 面板重新分析了 111 名 RT 儿童和 32 名父母的种系 DNA，以识别传统低灵敏度方法未检测到的基因内变异。获得了 77 名患者的随访数据。发现了 9 例之前未检测到的嵌合病例，队列中共有 17/280 名患者存在嵌合变异 (6.1%)，变异等位基因频率在 0.9% 至 33% 之间，从而突出了之前的情况低估了其流行率。随访数据显示，七分之四的具有嵌合变异的幸存者出现了独特的新肿瘤，其中两个与初始肿瘤共享 SMARCB1 改变，强调了 SMARCB1 嵌合体的潜在临床影响。迄今为止，放疗中 SMARCB1 嵌合体的低估率强调了需要优化遗传咨询和肿瘤监测。考虑到 RT 的可怕预后，这些发现具有重大的医学意义。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by bi-allelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome (RTPS1). With increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable. This study focuses on exploring SMARCB1 germline alterations, notably mosaicism in blood samples of children with RT and in parents, using a custom NGS panel.A cohort of 280 children and 140 parents with germline analysis was studied. Germline DNA from 111 children with RT and 32 parents were re-analyzed with a custom NGS panel with 1,500X average depth targeting the SMARCB1 gene to identify intragenic variants not detected with conventional low-sensitivity methods. Follow-up data was obtained for 77 patients.Nine previously undetected mosaicism cases were identified, totaling 17/280 patients with a mosaic variant (6.1%) in the cohort, with variant allele frequencies between 0.9% and 33%, thus highlighting the prior underestimation of its prevalence. Follow-up data showed that 4 out of 7 survivors with mosaic variants developed distinct novel tumors, two sharing SMARCB1 alterations with the initial tumor, emphasizing the potential clinical impact of SMARCB1 mosaicism.The hitherto underestimated rate of SMARCB1 mosaicism in RT underscores the need for optimized genetic counseling and oncological monitoring. The findings have significant medical implications, considering the dire prognosis of RT.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.