Ergin, Volkan; Erdoğan, Mutlu; Yaşar, Ekrem; Zheng, Sika

Background/aim: Fibroblast Growth Factor Receptor (FGFR) gene fusions are recognized as pivotal oncogenic drivers, contributing to cancer initiation and progression across diverse malignancies. These fusions often represent significant therapeutic targets, particularly in challenging malignancies like cholangiocarcinoma. This study aimed to characterize the novel FGFR2::SHTN1 fusion, identify it as a de novo chimeric protein, and elucidate its precise oncogenic mechanism. Materials and methods: FGFR2::SHTN1 fusions were identified via cancer genomics databases and modeled using AlphaFold and HADDOCK. SHTN1 variants were expressed in Neuro-2a cells for coimmunoprecipitation, purification, and native polyacrylamide gel electrophoresis to assess oligomerization. Structural modeling included membrane embedding with Chemistry at HARvard Macromolecular Mechanics–Graphical User Interface (CHARMM–GUI). Results: We found that FGFR2::SHTN1 is an in-frame fusion formed by the joining of upstream FGFR2 exons 1–17 with downstream SHTN1 exons 7–17 in human, resulting in a chimeric protein retaining the intact FGFR2 tyrosine kinase domain. Our analyses revealed that Shootin1 inherently forms oligomers through its coiled–coil domains, which, within the fusion, mediate ligand-independent dimerization and constitutive activation of FGFR2. Conclusion: Our findings establish FGFR2::SHTN1 as a potent oncogenic driver in various cancers, particularly in cholangiocarcinoma, highlighting a unique mechanism of constitutive activation mediated by Shootin1’s CCD-II domain. This study represents the first molecular characterization of the FGFR2::SHTN1 fusion, advances understanding of FGFR2 fusion biology, and identifies a particular target for future diagnostic and therapeutic strategies in relevant malignancies.

Mavi, Ahmet; Yiğit, Nimet; Yiğit, Demet; Kandemir, Ali

Sonchus erzincanicus (Asteraceae) is a plant species that is endemic to Turkey and grows in Erzincan. Lipid peroxidation inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and total phenolic content of the methanol and water extracts of the plant were determined. Antimicrobial activity of the extracts was also tested against 107 clinical isolates of human pathogenic microorganism strains belonging to Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus,and Candida albicans using the disc-diffusion method, and the minimal inhibition concentration (MIC) value of each active extract was determined. The extracts were observed to have antioxidant potential, although no better than that of BHT (butylated hydroxytoluene), which is a well- known commercial antioxidant. The extracts exhibited antimicrobial effects on all the tested microorganism species, except for P. aeruginosa and E. aerogenes. In addition, antifungal activity of the methanol extract against C. albicans was better than that of the water extract (inhibition zone: 25 mm; MIC: 0.156 mg/mL). As a consequence, it was observed that the methanol and water extracts of Sonchus erzincanicus had in vitro lipid peroxidation inhibition and antimicrobial effects against some microorganisms.

Mavi, Ahmet; Yiǧit, Nimet; Yiǧit, Demet; Kandemir, Ali

Sonchus erzincanicus (Asteraceae) is a plant species that is endemic to Turkey and grows in Erzincan. Lipid peroxidation inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and total phenolic content of the methanol and water extracts of the plant were determined. Antimicrobial activity of the extracts was also tested against 107 clinical isolates of human pathogenic microorganism strains belonging to Enterobacter aerogenes, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans using the disc-diffusion method, and the minimal inhibition concentration (MIC) value of each active extract was determined. The extracts were observed to have antioxidant potential, although no better than that of BHT (butylated hydroxytoluene), which is a wellknown commercial antioxidant. The extracts exhibited antimicrobial effects on all the tested microorganism species, except for P. aeruginosa and E. aerogenes. In addition, antifungal activity of the methanol extract against C. albicans was better than that of the water extract (inhibition zone: 25 mm; MIC: 0.156 mg/mL). As a consequence, it was observed that the methanol and water extracts of Sonchus erzincanicus had in vitro lipid peroxidation inhibition and antimicrobial effects against some microorganisms.