Thorner Paul Scott, Chong Anne-Laure, Jung Sung Mi, Fox Gabriel P P, Corbally Martin, Foulkes William D
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Virchows Arch. 2025 Jul 12. doi: 10.1007/s00428-025-04180-9.
DICER1-related tumor predisposition is an inherited disorder, generally pediatric in onset, featuring a characteristic array of mainly mesenchymal tumors. We report a chest wall desmoid fibromatosis, occurring in a child who uniquely carries a germline "hotspot" DICER1 variant that likely leads to impaired miRNA biogenesis in all cells. This lesion contained a hotspot CTNNB1 c.134C > T, (p.S45F) exon 3 somatic mutation and immunohistochemistry showed nuclear accumulation of β-catenin. Desmoid fibromatosis is known to be associated with dysregulation of β-catenin, resulting from altered APC or CTNNB1, leading to increased WNT pathway signaling. In fetal lung tumors linked to DICER1 hotspot variants, APC and/or CTNNB1 somatic mutations are found in most cases, suggesting a synergistic effect with DICER1 hotspot mutation to increase WNT pathway signaling. We postulate a similar mechanism is involved in this case and that desmoid fibromatosis is a rare mesenchymal lesion that could be part of DICER1-related tumor predisposition.
与DICER1相关的肿瘤易感性是一种遗传性疾病，通常在儿童期发病，其特征是一系列主要为间充质肿瘤。我们报告了一例胸壁韧带样纤维瘤病，发生在一名独特地携带种系“热点”DICER1变异的儿童身上，该变异可能导致所有细胞中的微小RNA生物合成受损。该病变包含热点CTNNB1 c.134C>T，（p.S45F）外显子3体细胞突变，免疫组织化学显示β-连环蛋白在细胞核中积聚。已知韧带样纤维瘤病与β-连环蛋白的失调有关，这是由APC或CTNNB1改变引起的，导致WNT信号通路增加。在与DICER1热点变异相关的胎儿肺肿瘤中，大多数病例都发现了APC和/或CTNNB1体细胞突变，这表明与DICER1热点突变有协同作用，可增加WNT信号通路。我们推测本例涉及类似机制，并且韧带样纤维瘤病是一种罕见的间充质病变，可能是与DICER1相关的肿瘤易感性的一部分。
