Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant central nervous system tumor predominantly affecting infants. Mutations of SMARCB1 or (rarely) SMARCA4 causing loss of nuclear SMARCB1 or SMARCA4 protein expression are characteristic features, but further recurrent genetic alterations are lacking. Most AT/RTs occur de novo, but secondary AT/RTs arising from other central nervous system tumors have been reported. Malignant gliomas, IDH wild-type, arising in patients with Li-Fraumeni syndrome typically show somatic mutations of TP53 as well as complex copy number alterations, but little is known about the loss of SMARCB1 or SMARCA4 protein expression in this context. Here, we report 2 children in whom malignant supratentorial brain tumors with SMARCB1 deficiency, complex copy number alterations, and somatic TP53 mutations lead to the discovery of pathogenic/likely pathogenic TP53 variants in the germline. Screening of the molecularneuropathology.org dataset for cases with similar genetic and epigenetic alterations yielded another case with SMARCA4 deficiency in a young adult with Li-Fraumeni syndrome. In conclusion, SMARCB1-deficient or SMARCA4-deficient malignant brain tumors with complex copy number alterations and somatic TP53 mutations in children and young adults may represent the first clinical manifestation of Li-Fraumeni syndrome and should prompt genetic counseling and investigation for TP53 germline status.

非典型畸胎样/横纹肌样瘤 (AT/RT) 是一种主要影响婴儿的恶性中枢神经系统肿瘤。SMARCB1或（很少）SMARCA4突变导致核 SMARCB1 或 SMARCA4 蛋白表达丧失是特征性特征，但缺乏进一步的复发性遗传改变。大多数 AT/RTs 是从头发生的，但也有报道称由其他中枢神经系统肿瘤引起的继发性 AT/RTs。在 Li-Fraumeni 综合征患者中出现的 IDH 野生型恶性神经胶质瘤通常显示TP53的体细胞突变以及复杂的拷贝数改变，但在这种情况下对 SMARCB1 或 SMARCA4 蛋白表达的丧失知之甚少。在这里，我们报告了 2 名患有 SMARCB1 缺陷、复杂拷贝数改变和体细胞TP53突变的恶性幕上脑肿瘤导致在生殖系中发现致病性/可能致病性TP53变异的儿童。通过对具有相似遗传和表观遗传改变的病例的分子神经病理学.org 数据集进行筛选，发现另一例患有 Li-Fraumeni 综合征的年轻成人患有 SMARCA4 缺乏症。总之，SMARCB1 缺陷或 SMARCA4 缺陷的恶性脑肿瘤具有复杂的拷贝数改变和体细胞TP53儿童和年轻人的突变可能代表 Li-Fraumeni 综合征的第一个临床表现，应及时进行遗传咨询和调查TP53种系状态。