DICER1 (Dicer 1 Ribonuclease III)

Genome-wide analyses identified candidate modifier loci functionally linked to PTEN, including in ZNF713, TPTE2P1, and PDPK1. These findings demonstrate that PHTS phenotypes are shaped by complex gene-gene interactions beyond PTEN alone, informing mechanisms underlying the cancer-NDD dichotomy and advancing precision risk stratification.

However, in SCT the DICER1 expression is common, but unrelated to DICER1 mutation. This suggests that alternative mechanisms, potentially involving androgen-related pathways, may contribute to DICER1 expression in these tumors.

Multiple gene mutations, in addition to DICER1 gene mutation, may influence the behavior and prognosis of DICER1 syndrome. We detail the necessity of instituting personalized, multidisciplinary monitoring plans, including regular clinical evaluations and targeted imaging of high-risk organs, to enable early detection and intervention.

Herein, we report a pediatric case of a presacral tumor classified as a teratoid medulloepithelioma with genetic and epigenetic charaterizations. Using DNA-methylation profiling analysis, the tumor was classified between ETMR, non C19MC-altered, and intra-ocular medulloepithelioma, arguing for a potential distinct cell origin, not represented in the current epigenetic classifiers.

DICER1-related primitive polyphenotypic neoplasms present significant diagnostic difficulty due to their varied appearances and lack of consistent nomenclature in the rare reports to date. Recognition of the morphologic features of these unusual neoplasms should prompt confirmatory DICER1 testing and consideration of germline evaluation, particularly in young patients.

Such mutations disrupt RNA cleavage fidelity, destabilize domain architecture or hinder small RNA loading, leading to cancers and developmental disorders, including Wilms tumor, DICER1 syndrome, myelodysplastic syndromes and Lessel-Kreienkamp syndrome. This Review highlights the structural basis of these pathogenic mutations and discusses how emerging insights from structural biology are shaping our understanding of RNA interference-related disease mechanisms and guiding potential therapeutic strategies.

She was successfully treated with ultrasound-guided microwave ablation, and we describe her clinical course in detail. This case underscores the importance of considering DICER1 syndrome in young patients with FND and illustrates that microwave ablation can be a safe and effective therapeutic option.

ENX increases the abundance of tumor-suppressive miRNAs and downregulates oncogenic pathways, including pathways related to cell cycle progression, angiogenesis, and cell migration. These results establish the essential role of miRNA biogenesis in suppressing AS and reveal a pharmacologically targetable vulnerability via ENX-mediated enhancement of miRNA expression in tumors.

This case underscores the diagnostic importance of recognizing ovarian SPN and its potential for aggressive behavior. Awareness of its morphologic, immunophenotypic, and molecular features is essential for distinction from other ovarian tumors.

In addition, a pathogenic TP53 mutation was detected exclusively in the high-grade area. This case represents only the second documented ovarian SLCT with confirmed high-grade transformation supported by a concurrent TP53 alteration.

The study underscores the heterogeneity in age and clinical presentation at the time of CLM diagnosis, highlighting the importance of an individualized and tailored approach to management.