在编码ATP依赖性染色质重塑蛋白SMARCA4(以前称为BRG1)的基因SMARCA4中，杂合生殖系致病变异(GPVs)会引起多种罕见肿瘤类型的易感性，包括卵巢小细胞癌、高钙型、非典型畸胎瘤、恶性横纹肌肿瘤和子宫肉瘤。近年来，对SMARCA4进行的生殖系检测增加，揭示了影响患有其他癌症类型的患者的可疑GPVs。在这里，我们描述了11例神经母细胞瘤(NBL)患者（包括4个先前未报道的案例），所有这些患者都发现携带SMARCA4的杂合生殖细胞变异体。平均诊断年龄为5岁(范围为2个月至26年)；九个是男性；其中八个患者的肿瘤位置信息在肾上腺。其中八个生殖系变异体预期会导致SMARCA4的功能丧失(大片段缺失、截短和规范剪接变异)，而其余四个是错义变异体。所有进行体细胞检测的八个案例中都发现野生型SMARCA4等位基因缺失性失调，支持SMARCA4作为经典肿瘤抑制因子的观点。总之，这些发现强烈表明NBL应该包含在SMARCA4相关肿瘤的范围内。©2023 作者(或其雇主)。未经授权，不得进行商业再利用。BMJ出版。

Heterozygous germline pathogenic variants (GPVs) in SMARCA4, the gene encoding the ATP-dependent chromatin remodelling protein SMARCA4 (previously known as BRG1), predispose to several rare tumour types, including small cell carcinoma of the ovary, hypercalcaemic type, atypical teratoid and malignant rhabdoid tumour, and uterine sarcoma. The increase in germline testing of SMARCA4 in recent years has revealed putative GPVs affecting SMARCA4 in patients with other cancer types. Here we describe 11 patients with neuroblastoma (NBL), including 4 previously unreported cases, all of whom were found to harbour heterozygous germline variants in SMARCA4 Median age at diagnosis was 5 years (range 2 months-26 years); nine were male; and eight of nine cases had tumour location information in the adrenal gland. Eight of the germline variants were expected to result in loss of function of SMARCA4 (large deletion, truncating and canonical splice variants), while the remaining four were missense variants. Loss of heterozygosity of the wild-type SMARCA4 allele was found in all eight cases where somatic testing was performed, supporting the notion that SMARCA4 functions as a classic tumour suppressor. Altogether, these findings strongly suggest that NBL should be included in the spectrum of SMARCA4-associated tumours.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.