Ciceri Sara, Bertolotti Alessia, Serra Annalisa, Gattuso Giovanna, Boschetti Luna, Capasso Maria, Cecchi Cecilia, Sorrentino Stefania, Quarello Paola, Ciniselli Chiara Maura, Verderio Paolo, De Cecco Loris, Manenti Giacomo, Diomedi Camassei Francesca, Collini Paola, Spreafico Filippo, Perotti Daniela
Predictive Medicine: Molecular Bases of Genetic Risk, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
Diagnostic and Molecular Research Lab, Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
iScience. 2024 Aug 6;27(9):110684. doi: 10.1016/j.isci.2024.110684. eCollection 2024 Sep 20.
Few studies investigated the genetics of relapsed Wilms tumor (WT), suggesting the gene, the microRNA processing genes, and the MYCN network as possibly involved in a relevant percentage of relapses. We investigated 28 relapsing WT patients (10 new cases and 18 cases in which the involvement of and miRNAPG had been excluded) with a panel of ∼5000 genes. We identified variants affecting genes involved in DNA damage prevention and repair in 12/28 relapsing patients (42.9%), and affecting genes involved in chromatin modification and regulation in 6/28 relapsing patients (21.4%), widening the spectrum of anomalies detected in relapsed tumors. The disclosure of molecular pathways possibly underlying tumor progression might allow to use molecularly targeted therapies at relapse. Surprisingly, germline anomalies, mostly affecting DNA damage prevention and repair genes, were identified in 13/28 patients (46.4%), raising the issue of performing a genetic testing to all children presenting with a WT.
很少有研究调查复发性肾母细胞瘤（WT）的遗传学，提示某些基因、微小RNA加工基因以及MYCN网络可能在相当比例的复发中起作用。我们用一个包含约5000个基因的检测板对28例复发性WT患者（10例新发病例和18例已排除特定基因和微小RNA加工基因参与的病例）进行了研究。我们在12/28例（42.9%）复发性患者中鉴定出影响参与DNA损伤预防和修复的基因的变异，在6/28例（21.4%）复发性患者中鉴定出影响参与染色质修饰和调控的基因的变异，拓宽了在复发性肿瘤中检测到的异常谱。揭示可能是肿瘤进展基础的分子途径可能有助于在复发时使用分子靶向治疗。令人惊讶的是，在13/28例（46.4%）患者中鉴定出种系异常，主要影响DNA损伤预防和修复基因，这就提出了对所有患WT的儿童进行基因检测的问题。
