肺母细胞瘤是一种罕见的、双相的、成人发病的肺肿瘤。在这项研究中，我们通过深入分析定义肺母细胞瘤的分子事件来研究 DICER1 致病性变异是否是肺母细胞瘤的一个特征。我们对来自 6 名受影响者的 8 个肺母细胞瘤进行了全外显子组测序和 DNA 甲基化分析。我们鉴定了双等位基因8 例中有 7 例存在体细胞 DICER1 致病性变异。其余病例在 DICER1 的 RNase IIIb 结构域中存在孤立的错义致病性变异。 8 例中有 6 例携带 CTNNB1 热点变异，8 例中有 4 例携带 TP53 体细胞致病性变异。甲基化分析显示，肺母细胞瘤与其他 DICER1 突变肿瘤聚集在一起，而不是与其他更常见类型的肺癌聚集在一起。我们得出结论，体细胞 DICER1 致病性变异是肺母细胞瘤的主要驱动因素，并且可能与 CTNNB1 热点变异一起发挥作用。经常出现。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Pulmonary blastoma is a rare, biphasic, adult-onset lung tumor. In this study, we investigate whether DICER1 pathogenic variants are a feature of pulmonary blastomas through in-depth analysis of the molecular events defining them.We performed exome-wide sequencing and DNA methylation profiling of 8 pulmonary blastomas from 6 affected persons.We identified biallelic somatic DICER1 pathogenic variants in 7 of 8 cases. The remaining case had a solitary missense pathogenic variant in the RNase IIIb domain of DICER1. Six of 8 cases carried a CTNNB1 hotspot variant and 4 of 8 had a somatic pathogenic variant in TP53. Methylation analysis showed that the pulmonary blastomas clustered with other DICER1-mutated tumors and not with other more common types of lung cancer.We conclude somatic DICER1 pathogenic variants are the major driver of pulmonary blastoma and are likely to act in conjunction with CTNNB1 hotspot variants that are often present.Copyright © 2024 Elsevier B.V. All rights reserved.