Current Issue : April-June Volume : 2026 Issue Number : 2 Articles : 5 Articles
Background: Complex cases of retinoblastoma (RB) often require integrative molecular approaches to define tumor etiology and guide clinical management. Purpose: Our aim was to evaluate the usefulness of combining aqueous humor (AH)/plasma cell-free DNA next-generation sequencing (cfDNA-NGS) and long-read–whole-genome sequencing (LR-WGS) to resolve diagnostically challenging RB cases. Case Description: We report the case of a 3-year-old Caucasian girl, conceived by heterologous assisted reproductive technology (ART), presenting with unilateral, widely infiltrative RB in the right eye. She exhibited limited verbal communication, a glabellar angioma extending to the nasal bridge and philtrum, and mild hypertelorism. Standard blood testing revealed no pathogenic SNVs, CNVs, or methylation abnormalities in the RB1 gene. Targeted cfDNA analysis using the Illumina TruSight Oncology 500 (TSO500) panel on AH and plasma identified a somatic RB1 splice-site variant (c.1498+2T>C) with a variant allele frequency (VAF) of 98.5%, consistent with biallelic inactivation. Additional gains (fold change > 1.5) were found in AH and confirmed in plasma, suggesting a germline 13q duplication. Third-generation LR-WGS, performed with Oxford Nanopore Technology (ONT), on blood confirmed a 24.6 Mb duplication on chromosome 13, compatible with the rare 13q duplication syndrome characterized by psychomotor delay, craniofacial dysmorphism, and hemangiomas. AH-cfDNA revealed additional somatic copy-number alterations, including amplifications (i.e., MDM4 and ALK) and deletions (i.e., BRCA2), indicating progressive clonal tumor evolution. Conclusions: This experience tells us that a combined approach with TSO500 Illumina NGS on cfDNA, along with LR-WGS, is able to help solve complex cases and define the appropriate treatment and surveillance strategy....
Background/Objectives: Satellite DNAs (satDNAs) are tandemly repeated sequences that play essential roles in chromosome structure, genome organization, and evolution. Despite their importance, the satellitome (the complete collection of satDNAs) of most avian lineages remains unexplored. We sought to describe the repeatome of three trogonid species, Trogon surrucura, T. melanurus, and Apaloderma vittatum with a focus on the satellitome to evaluate the general features of this lineage. Methods: Herein, we provide the first comparative characterization of the repeatome, with a particular focus on the comparative characterization of satDNAs in three trogonid species: T. surrucura, T. melanurus, and A. vittatum. Using a combination of bioinformatic pipelines and cytogenetic approaches. Results: We identified 16 satDNA families in T. surrucura, 15 in T. melanurus, and only 3 in A. vittatum. Sequence comparisons revealed that five families are shared between the two Trogon species, consistent with the library hypothesis, whereas no satDNAs were shared with A. vittatum. While both Trogon species exhibited a predominance of GC-rich repeats, A. vittatum represents the first bird described with a satellitome dominated by AT-rich satDNAs. In situ mapping in T. surrucura revealed chromosome-specific satDNAs restricted to pairs 1 and 2 and a Z-specific repeat that was strongly accumulated on its long arms, an atypical feature among birds. Conversely, the W chromosome showed a surprisingly low number of satDNAs, limited to centromeric signals. Conclusions: Our results reveal highly divergent satellitome landscapes among trogonids, characterized by lineage-specific differences in repeat composition, abundance, and chromosomal distribution. These findings support the view that satDNAs are dynamic genomic elements, whose amplification, loss, and chromosomal redistribution can influence genome architecture and play a role in avian speciation....
Background: Keloid is a common pathological scar tissue, which invades the surrounding normal skin and leads to symptoms such as pain, pruritus, erythema, and edema, thereby impacting the quality of life. In this study, we conducted bioinformatics analysis of keloid fibroblasts and normal skin tissue to identify DEGs and the pathways involved in the mechanism of keloid fibroblast proliferation. Methods: GSE145725 was downloaded from the Gene Expression Omnibus (GEO) database, including nine keloid fibroblasts and 10 normal tissue fibroblast samples. GSE158395 included four lesional and three nonlesional samples from keloid patients, and six normal skin tissue samples were also evaluated. Through bioinformatics analysis, we established diagnosis model, and at the same time, we predicted therapeutic targets in the DSigDB database. Results: Six key genes were screened out by bioinformatics analysis, including BMP4, SPP1, HIF1α, POSTN, WNT5A, and SMAD3. Subsequently, three of these genes (BMP4, POSTN, and WNT5A) were found to be significantly associated with keloids. Paricalcitol and phosphine were identified as potential therapeutic candidates. Conclusions: This study identified three hub genes—BMP4, POSTN, and WNT5A—that are closely linked to keloid fibroblast hyperplasia and may serve as potential biomarkers for inhibiting keloid fibroblast hyperplasia. Further molecular and animal studies are needed to fully understand the mechanisms of keloid development....
Objective: Given the crucial roles of GSK-3β in epithelial–mesenchymal transition (EMT), we assume that it may also be involved in tumor stemness, immune evasion, and drug resistance in triple-negative breast cancer (TNBC). This study was designed to analyze the expression and clinical significance of GSK-3β and investigate its association with tumor stemness–related and immune-related genes. Methods: GSK-3β expression and clinical data of TNBC patients were obtained from TCGA. Survival analysis, differential gene expression, and gene set enrichment analysis (GSEA) were performed to explore associations between GSK-3β and tumor stemness, immune response, and clinical outcomes in TNBC. Immune cell infiltration was assessed using xCell, and key GSK-3β- related proteins were validated via parallel reaction monitoring–based proteomics. Results: GSK-3β expression was significantly upregulated in TNBC and was associated with poorer overall survival. In TNBC, 24 GSK-3β-associated genes linked to tumor stemness and immune response were identified, all of which were downregulated in the high GSK-3β expression group. Proteomic analysis further validated differential expression of key proteins, including upregulation of SERPINB2, KIT, and NOTCH1 and downregulation of DNMT1, MAPK1, and EP300 in GSK-3β- overexpressing cells. Conclusion: GSK-3β overexpression was associated with poor prognosis and was found to influence tumor stemness, immune modulation, and key signaling pathways that drive tumor progression and therapeutic resistance....
Primary liver cancer (PLC) and metformin are not well understood to be associated. We conducted a Mendelian randomization (MR) analysis using genetic data from IEU OpenGWAS and FinnGen R10, with metformin as the exposure and PLC as the outcome. The inverse variance weighting (IVW) method was the primary analytical approach, with heterogeneity assessed by Cochran's Q test, pleiotropy by MR- Egger intercept, and outliers by MR- PRESSO. Bioinformatics analyses further explored potential mechanisms, including differential gene expression, protein–protein interactions (PPI), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, immune cell infiltration analysis, and drug sensitivity analysis. MR results demonstrated a significant association between metformin use and reduced risk of PLC (β = −5.6046, OR = 0.0037, p = 0.026), with a Benjamini- Hochberg false discovery rate (FDR) adjusted p value of 0.13. However, no causal effect was observed for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC). By cross- referencing transcriptome data from the GEO database GSE241466 with metformin- related gene loci, 34 overlapping genes were identified. Differentially expressed genes (DEGs) were filtered using |log2FC| > 0 and p < 0.05, with five hub genes (DDX52, KIF11, GCDH, MRPL45, and TICRR) being particularly prominent. Functional enrichment analysis revealed involvement in cGMP- PKG signaling and fatty acid metabolism pathways. Further validation with GEPIA2, TIMER, and TISCH showed correlations between these genes and immune infiltration, while GSCA- based drug sensitivity analysis suggested therapeutic relevance. In summary, these findings indicate that metformin may reduce PLC risk by modulating metabolic and immune- related pathways, supporting its potential value as an adjunct therapeutic agent. However, further validation through large- scale clinical and basic research is warranted....
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