The fusion genes containing neuregulin-1 (NRG1) are newly described potentially actionable oncogenic drivers. Initial clinical trials have shown a positive response to targeted treatment in some cases of NRG1 rearranged lung adenocarcinoma, cholangiocarcinoma, and pancreatic carcinoma. The cost-effective large scale identification of NRG1 rearranged tumors is an open question. We have tested a data-drilling approach by performing a retrospective assessment of a de-identified molecular profiling database of 3263 tumors submitted for fusion testing. Gene fusion detection was performed by RNA-based targeted next-generation sequencing using the Archer Fusion Plex kits for Illumina (ArcherDX Inc., Boulder, CO). Novel fusion transcripts were confirmed by a custom-designed RT-PCR. Also, the aberrant expression of CK20 was studied immunohistochemically. The frequency of NRG1 rearranged tumors was 0.2% (7/3263). The most common histologic type was lung adenocarcinoma (n = 5). Also, renal carcinoma (n = 1) and prostatic adenocarcinoma (n = 1) were found. Identified fusion partners were of a wide range (CD74, SDC4, TNC, VAMP2, UNC5D), with CD74, SDC4 being found twice. The UNC5D is a novel fusion partner identified in prostate adenocarcinoma. There was no co-occurrence with the other tested fusions nor KRAS, BRAF, and the other gene mutations specified in the applied gene panels. Immunohistochemically, the focal expression of CK20 was present in 2 lung adenocarcinomas. We believe it should be considered as an incidental finding. In conclusion, the overall frequency of tumors with NRG1 fusion was 0.2%. All tumors were carcinomas. We confirm (invasive mucinous) lung adenocarcinoma as being the most frequent tumor presenting NRG1 fusion. Herein novel putative pathogenic gene fusion UNC5D-NRG1 is described. The potential role of immunohistochemistry in tumor identification should be further addressed.

• Klíčová slova
• EGF-like domain, ERBB, ERBB3, HER, HER 3, MAPK, NRG1, PIK, carcinoma, data drilling, gene fusion, gene rearrangement, genetics, lung, mRNA sequencing, molecular, neuregulin, next-generation sequencing, receptor heterodimerization, receptor tyrosine kinase,
• MeSH
• adenokarcinom genetika   patologie   MeSH
• antigeny diferenciační B-lymfocytární genetika   MeSH
• dospělí MeSH
• fúzní onkogenní proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránový protein 2 asociovaný s vezikuly genetika   MeSH
• MHC antigeny II. třídy genetika   MeSH
• nádory plic genetika   patologie   MeSH
• nádory prostaty genetika   patologie   MeSH
• neuregulin-1 genetika   MeSH
• receptory buněčného povrchu genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• syndekan-4 genetika   MeSH
• tenascin genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny diferenciační B-lymfocytární MeSH
• fúzní onkogenní proteiny MeSH
• invariant chain MeSH Prohlížeč
• membránový protein 2 asociovaný s vezikuly MeSH
• MHC antigeny II. třídy MeSH
• neuregulin-1 MeSH
• NRG1 protein, human MeSH Prohlížeč
• receptory buněčného povrchu MeSH
• SDC4 protein, human MeSH Prohlížeč
• syndekan-4 MeSH
• tenascin MeSH
• TNC protein, human MeSH Prohlížeč
• UNC5D protein, human MeSH Prohlížeč
• VAMP2 protein, human MeSH Prohlížeč

Neurodegenerative diseases are pathologies of the central and peripheral nervous systems characterized by loss of brain functions and problems in movement which occur due to the slow and progressive degeneration of cellular elements. Several neurodegenerative diseases are known such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and many studies on the molecular mechanisms underlying these pathologies have been conducted. Altered functions of some key proteins and the presence of intraneuronal aggregates have been identified as responsible for the development of the diseases. Interestingly, the formation of the SNARE complex has been discovered to be fundamental for vesicle fusion, vesicle recycling and neurotransmitter release. Indeed, inhibition of the formation of the SNARE complex, defects in the SNARE-dependent exocytosis and altered regulation of SNARE-mediated vesicle fusion have been associated with neurodegeneration. In this review, the biological aspects of neurodegenerative diseases and the role of SNARE proteins in relation to the onset of these pathologies are described.

• Klíčová slova
• ALS, Alzheimer’s disease, Parkinson’s disease, SNAP-25, SNAREs, VAMP2, neurodegenerative disease, syn1,
• MeSH
• exocytóza * MeSH
• fúze membrán * MeSH
• lidé MeSH
• nervový přenos * MeSH
• neurodegenerativní nemoci metabolismus   patofyziologie   MeSH
• proteiny SNARE metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• proteiny SNARE MeSH

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.

• MeSH
• Anaplasma phagocytophilum patogenita   MeSH
• bakteriální infekce imunologie   metabolismus   MeSH
• buněčné linie MeSH
• členovci metabolismus   mikrobiologie   fyziologie   MeSH
• Dermacentor metabolismus   mikrobiologie   fyziologie   MeSH
• extracelulární vezikuly metabolismus   ultrastruktura   MeSH
• Francisella tularensis patogenita   MeSH
• genová ontologie MeSH
• intravitální mikroskopie MeSH
• klíšťata metabolismus   mikrobiologie   MeSH
• klíště metabolismus   mikrobiologie   fyziologie   MeSH
• kůže imunologie   mikrobiologie   parazitologie   MeSH
• lidé MeSH
• membránový protein 2 asociovaný s vezikuly metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• proteiny R-SNARE metabolismus   MeSH
• proteomika MeSH
• T-lymfocyty metabolismus   MeSH
• tandemová hmotnostní spektrometrie MeSH
• transmisní elektronová mikroskopie MeSH
• zánět imunologie   metabolismus   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• membránový protein 2 asociovaný s vezikuly MeSH
• proteiny R-SNARE MeSH