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Povzetek: Giant cutaneous melanoma is a rare presentation characterized by significant morbidity and mortality. We report the case of a 45-year-old male presenting with an acute life-threatening hemorrhage from a giant melanoma on his right thigh. The tumor, measuring 90 × 50 × 85 mm, was immediately excised under local anesthesia to achieve hemostasis. The patient exhibited acute anemia and required postoperative blood transfusion. Histopathological analysis confirmed superficial spreading melanoma with a Breslow thickness of 85.0 mm and extensive ulceration. Genetic testing identified critical mutations, including BRAFV600D and alterations involving the ARID2, CDKN2A/B, AKT3, PTEN, and HRAS genes. Remarkably, no metastatic disease was detected upon thorough diagnostic evaluation. The patient received adjuvant immunotherapy with programmed cell death-1 inhibitors. Six months after the procedure, he remains free of metastasis. This case underscores the urgent need for timely recognition and intervention in giant melanoma with acute complications. It also highlights the effectiveness of modern adjuvant therapies in improving prognosis.
Ključne besede: dermatologic surgery, dermatopathology, melanoma, skin cancer
Objavljeno v DiRROS: 02.07.2026; Ogledov: 317; Prenosov: 226
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Povzetek: Craniopharyngiomas (CPs) are rare benign brain tumors that are classified as WHO grade I, with two subtypes: adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP). ACP is caused by somatic mutations in exon 3 of the CTNNB1 gene activating the Wnt signaling pathway. PCP is associated with somatic BRAF p.V600E mutations activating the MAPK signaling pathway. Understanding their molecular differences is crucial for diagnosis and treatment. This study aimed to analyze common somatic alterations in ACP and PCP using bulk transcriptome sequencing and in situ spatial transcriptomics. RNA sequencing and high-resolution spatial profiling were used to detect mutations and examine gene expression differences among ACP, PCP, and healthy pituitary tissue. Whole transcriptome sequencing was performed on 24 tumor samples, with healthy pituitary data from the GTEx portal. Bioinformatics analysis utilized the CTAT mutation pipeline, with Sanger sequencing for validation. Results confirmed BRAF p.V600E mutations in all PCP samples and CTNNB1 mutations in all ACP samples. Differential gene expression analysis highlighted distinct molecular profiles and reinforced the involvement of Wnt and MAPK signaling. Spatial profiling identified 41 differentially expressed genes between ACP and PCP. This study provides critical insights into CP biology, supporting improved diagnostics and potential therapeutic strategies.
Ključne besede: craniopharyngioma, differential gene expression, in situ spatial profiling, somatic mutation detection, transcriptional analysis
Objavljeno v DiRROS: 10.04.2026; Ogledov: 279; Prenosov: 213
Celotno besedilo (2,18 MB)
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Povzetek: Alport syndrome (AS) is a genetically heterogeneous disorder caused by mutations in COL4A3, COL4A4, or COL4A5, leading to progressive renal dysfunction. While genetic screening has advanced, many cases remain undiagnosed due to deep intronic splice site variants. We report a male patient diagnosed with autosomal recessive AS, characterized by hematuria, proteinuria, and chronic kidney disease progression. Initial kidney biopsy at age 10 revealed glomerular basement membrane thinning and focal sclerosis, while targeted DNA sequencing failed to detect pathogenic variants. Over 15 years, renal function declined, and a second biopsy showed severe GBM abnormalities with multilamellated structures. Whole-transcriptome sequencing revealed two events of exon skipping, specifically at exons 27 and 38 of the COL4A4 gene, which were verified by exon-specific PCR and Sanger sequencing. Intronic regions analysis revealed two heterozygous variants positioned 78 bp downstream of exon 27 and 8 bp upstream of exon 38, though their role in aberrant splicing remains uncertain. Immunofluorescence analysis confirmed disrupted α3α4α5(IV) heterotrimer assembly. This is the first documented case of dual exon-skipping events in COL4A4, highlighting their contribution to disease severity. Our findings emphasize the need for RNA-based diagnostics and raise questions about potential benefit of exon-skipping therapy in autosomal recessive AS.
Ključne besede: Alport syndrome, exon skipping, whole transcriptome sequencing, kidney, COL4A4
Objavljeno v DiRROS: 24.11.2025; Ogledov: 925; Prenosov: 354
Celotno besedilo (3,18 MB)
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Povzetek: Glioblastoma (GB) is the most common primary malignant brain tumor, characterized by resistance to therapy. Despite aggressive treatment options, GB remains an incurable disease. Invasiveness and heterogeneity are key GB features that cannot be studied in preclinical in vitro models. In this study, we investigated the effects of standard therapy using patient-derived GB organoids (GBOs). GBOs reflect the complexity and heterogeneity of the original tumor tissue. No significant effect on GBO viability or invasion was observed after irradiation and temozolomide treatment. E3 ubiquitin-protein ligase (MDM2), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the serine/threonine kinases ATM and ATR were upregulated at the gene and protein levels after treatment. Our results show that the p53 pathway and DNA-damage response mechanisms were triggered, suggesting that GBOs recapitulate GB therapy resistance. GBOs thus provide a highly efficient platform to assess the specific responses of GB patients to therapy and to further explore therapy resistance.
Ključne besede: cellular physiology, cellular toxicology, in vitro toxicology including 3D culture, technical aspects of cell biology, cancer
Objavljeno v DiRROS: 09.09.2024; Ogledov: 1590; Prenosov: 838
Celotno besedilo (9,14 MB)
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Povzetek: Background. Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also con- tributes to cell's malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms. The aim of our study was to search new gliomagenesis-specific candidate lncRNAs involved in epigenetic regulation. Patients and methods. We used a microarray approach to detect expression profiles of epigenetically involved lncRNAs on a set of 12 glioma samples, and selected LOC285758 for further qPCR expression validation on 157 glioma samples of different subtypes. To establish if change in expression is a consequence of epigenetic alterations we determined methylation status of lncRNA's promoter using MS-HRM. Additionally, we used the MLPA analysis for de- termining the status of known glioma biomarkers and used them for association analyses. Results. In all glioma subtypes levels of LOC285758 were significantly higher in comparison to normal brain reference RNA, and expression was inversely associated with promoter methylation. Expression substantially differs between astrocytoma and oligodendroglioma, and is elevated in higher WHO grades, which also showed loss of methylation. Conclusions. Our study revealed that lncRNA LOC285758 changed expression in glioma is methylation-dependent and methylation correlates with WHO malignancy grade. Methylation is also distinctive between astrocytoma I-III and other glioma subtypes and may thus serve as an additional biomarker in glioma diagnosis.
Ključne besede: glioma, epigenetics, methylation
Objavljeno v DiRROS: 03.06.2024; Ogledov: 1402; Prenosov: 955
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