DCTN1 (Dynactin Subunit 1)

Genomic metrics showed tumor mutational burden (TMB) of 0.94/Mb, microsatellite stability, and CNV burden of 2.1%. He underwent near total resection followed by alectinib; to our knowledge, this is the first reported young pediatric (<10 years old) CNS IMT with this fusion.

The remaining 343 transcripts did not show consistent expression patterns in the cell lines, suggesting their dysregulation in patient-derived tissues may be due to the stromal or microenvironmental factors absent in vitro. In summary, this comparative transcriptomic analysis identified 32 transcript isoforms, comprising 2 canonical and 30 non-canonical transcripts, that may play regulatory roles in colon carcinogenesis and warrant further investigation in the context of gut epithelial cell biology.

This report describes the first case of gastric adenocarcinoma harboring a DCTN1-ALK fusion that was successfully treated with the ALK-targeted agent alectinib after first- and second-line chemotherapy-based regimens had failed...The other documented cases with DCTN1-ALK fusion treated with the first or second generation of ALK inhibitors indicated this rare fusion as an actionable driver gene mutation. This successful personalized anti-tumor strategy highlights the clinical utility of comprehensive genomic profiling and liquid biopsy in detecting and monitoring actionable ALK fusions in solid tumors.

The predominance of FN1::ALK fusions, sharing identical breakpoints (ALK exons 18 to 19) with pseudosarcomatous myofibroblastic proliferations of the urinary bladder, alongside expanded molecular diversity (non-FN1/ROS1 fusions), supports their classification as a biological continuum of ALK-driven bladder mesenchymal neoplasms. These findings broaden the molecular genetic spectrum of bladder IMTs and advocate for histology-guided molecular testing to identify kinase fusions, reinforcing conservative management for these typically indolent tumors.

Furthermore, we identified NACAD as an independent prognostic factor for both GBM OS and DSS. In summary, comprehensive analysis of methylation and transcriptome data led to the identification of genes and pathways in different GBM subtypes, highlighting prognostic genes and ceRNA regulatory networks, and proposing potential candidates.

With follow-up periods of 4-30 months post complete resection, all patients remained disease-free. These findings expand the recognized morphologic spectrum of cutaneous and superficial mucosal ALK-rearranged IMTs while underscoring the indispensable role of integrated histopathologic and molecular pathologic evaluation in differentiating these neoplasms from their histologic mimics, such as inflammatory rhabdomyoblastic tumor, non-neural granular cell tumor, and epithelioid fibrous histiocytoma/superficial ALK-rearranged myxoid spindle cell neoplasm.

Our case serves as a great addition to the limited number of cases reported in the literature, and it represents the first published pediatric case with the rare DCTN1::ALK fusion. The novelty of this genetic alteration and the lack of knowledge about its potential effects on the clinical aspects of ALK-positive histiocytosis highlight the importance of ancillary molecular testing, when available.

DCTN1-RET is a novel oncogenic fusion gene in thyroid cancer that promotes tumorigenesis through CC domain-mediated dimerization. It represents a potential therapeutic target for RET-specific inhibitors.

Patients with thoracic IMT patients are typically young with early-stage disease. ALK fusion were the most common genetic alteration, particularly in spindle-cell patterns. Characterization of the tumor microenvironment indicates the potential of immune profiling in the tumor biology and targeted immunotherapy approaches.

Furthermore, the analysis of clinical data provided compelling evidence that high levels of USP53 and NPY2R expression are closely linked to a poor prognosis for patients, suggesting that these proteins could serve as negative prognostic indicators. In contrast, low levels of DCTN1-AS1 expression were found to predict a poor response to treatment, further underscoring its importance in the context of therapy outcomes.