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Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor with a worse prognosis than Wilms' tumor. Although recently, BCOR internal tandem duplication (ITD) has been found as a driver mutation in more than 80% of cases, a deep molecular characterization of this tumor is still lacking, as well as its correlation with the clinical course. The aim of this study was to investigate the differential molecular signature between metastatic and localized BCOR-ITD-positive CCSK at diagnosis. Whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) were performed on six localized and three metastatic BCOR-ITD-positive CCSKs, confirming that this tumor carries a low mutational burden. No significant recurrences of somatic or germline mutations other than BCOR-ITD were identified among the evaluated samples. Supervised analysis of gene expression data showed enrichment of hundreds of genes, with a significant overrepresentation of the MAPK signaling pathway in metastatic cases ( p < 0.0001). Within the molecular signature of metastatic CCSK, five genes were highly and significantly over-expressed: FGF3, VEGFA, SPP1, ADM, and JUND. The role of FGF3 in the acquisition of a more aggressive phenotype was investigated in a cell model system obtained by introducing the ITD into the last exon of BCOR by Crispr/Cas9 gene editing of the HEK-293 cell line. Treatment with FGF3 of BCOR-ITD HEK-293 cell line induced a significant increase in cell migration versus both untreated and scramble cell clone. The identification of over-expressed genes in metastatic CCSKs, with a particular focus on FGF3, could offer new prognostic and therapeutic targets in more aggressive cases.

Necrotizing enterocolitis (NEC) is a gut inflammatory disorder which constitutes one of the leading causes of morbidity and mortality for preterm infants. The pathophysiology of NEC is yet to be fully understood; several observational studies have led to the identification of multiple factors involved in the pathophysiology of the disease, including gut immaturity and dysbiosis of the intestinal microbiome. Given the complex interactions between microbiota, enterocytes, and immune cells, and the limited access to fetal human tissues for experimental studies, animal models have long been essential to describe NEC mechanisms. However, at present there is no animal model perfectly mimicking human NEC; furthermore, the disease mechanisms appear too complex to be studied in single-cell cultures. Thus, researchers have developed new approaches in which intestinal epithelial cells are exposed to a combination of environmental and microbial factors which can potentially trigger NEC. In addition, organoids have gained increasing attention as promising models for studying NEC development. Currently, several in vitro models have been proposed and have contributed to describe the disease in deeper detail. In this paper, we will provide an updated review of available in vitro models of NEC and an overview of current knowledge regarding its molecular underpinnings.

Nowadays, thanks to extensive studies and progress in precision medicine, pediatric leukemia has reached an extremely high overall survival rate. Nonetheless, a fraction of relapses and refractory cases is still present, which are frequently correlated with poor prognosis. Although several molecular features of these diseases are known, still the field of energy metabolism, which is widely studied in adult, has not been frequently explored in childhood leukemias. Metabolic reprogramming is a hallmark of cancer and is deeply connected with other genetic and signaling aberrations generally known to be key features of both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This review aims to clear the current knowledge on metabolic rewiring in pediatric ALL and AML, also highlighting the influence of the main signaling pathways and suggesting potential ideas to further exploit this field to discover new prognostic biomarkers and, above all, beneficial therapeutic options.