https://hdl.handle.net/20.500.14178/904 2026-07-26T09:47:05Z https://hdl.handle.net/20.500.14178/3874 Clinicopathologic features of KRAS G12C-mutated non-small cell lung carcinomas:insights from 279 retrospective cases Bradová, Martina; Slavík, Petr; Vaněček, Tomáš; Martínek, Petr; Grossmann, Petr; Kormunda, Stanislav; Behenská, Kristýna; Svatoň, Martin; Pešek, Miloš; Jirásek, Tomáš; Špůrková, Zuzana; Hroudová, Petra; Mrázková, Hana; Hořavová, Barbora; Roubec, Jaromír; Baník, Martin; Mukenšnabl, Petr; Michal, Michal; Švajdler, Marián KRAS G12C-mutated non-small cell lung carcinoma (NSCLC), caused by a glycine-to-cysteine substitution at codon 12, is associated with poor prognosis and is now targetable with specific inhibitors. We retrospectively analyzed 279 KRAS G12C-mutated NSCLC cases (2017-2023) from our registry with available histologic, immunohistochemical, and molecular data. The cohort included 279 patients (125 females, 151 males; mean age 67 years, range 29-91). Most tumors were primary lung carcinomas (n = 229, 82%), while 45 (16%) were metastatic at presentation. Morphologic evaluation was available in 240 tumors: 37% showed solid squamous cell carcinoma (SCC)-like features, 61% rhabdoid/plasmacytoid morphology, and 17% sarcomatoid features. Adenocarcinoma-associated patterns were present in 67 cases, often mixed, and focal solid growth occurred in 77%. TTF1, Napsin A, and CK7 were positive in 86%, 87%, and 98%, respectively, whereas squamous markers were infrequent (p40/p63 7%, CK5/6 8%). PD-L1 expression was detected in 65%. Co-mutations most commonly involved TP53 (n = 27) and STK11 (n = 12); IDH1/2, PIK3CA, and CTNNB1 mutations occurred in four cases each, MET in two cases, and BRAF, FGFR2, FGFR3, and GNAS in one case each. Two gene fusions were identified (LRP12::NRG1, FGFR3::TACC3). Mean survival was 1.89 years, with one- and five-year survival rates of 54% and 25%. KRAS G12C-mutated NSCLC is clinically aggressive and frequently shows solid growth with rhabdoid, plasmacytoid, or SCC-like morphology, which may lead to misclassification and missed genetic testing. Immunohistochemistry and molecular profiling are essential for accurate classification and enabling targeted therapy. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3866 HERA: a web server for host element reference-based aligner Molano, Leidy-Alejandra G; Hirsch, Pascal; Keller, Andreas; Dolejská, Monika; Palkovičová, Jana Plasmids play a central role in bacterial adaptation and in the dissemination of antimicrobial resistance, driving a growing need for accessible tools that support their comparative analysis without requiring local computational infrastructure. Although several circular genome visualization platforms exist, most are designed for general bacterial genome analysis rather than focused on plasmid comparison. Host element reference-based aligner (HERA) is a web server for intuitive visualization and comparison of plasmids and other circular molecules through BLAST alignment against reference sequences. Built on interactive circular genome visualization, HERA simplifies comparative genomics by providing an accessible interface for exploring sequence similarity, identifying conserved regions, and analyzing genetic elements without the complexity of traditional local tools. HERA includes a plasmid-oriented annotation pipeline covering replicon and mobility typing, antimicrobial resistance detection, mobile element identification, and homology search against the PLSDB plasmid database. HERA also provides an automatic selection of the reference which is the most appropriate from the uploaded sequences. The web server is available without login or any restriction at https://web.ccb.uni-saarland.de/hera/. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3865 Comparison of microbial profiles between hospital wastewater and river water Gagaletsios, Lazaros A; Sourenian, Tsolaire; Karpouzas, Dimitrios; Bitar, Ibrahim; Papagiannitsis, Costas This study aimed to compare the microbial profiles between hospital wastewater and river water to assess the dissemination of clinical isolates into the environment. Two types of water samples were collected from sampling sites which were geographically close (wastewater from the University Hospital of Larissa and river water from the Pineios River). Gram-negative bacteria isolated from both sample types were identified using MALDI-TOF. Furthermore, the minimum inhibitory concentration (MIC) of antibiotics were evaluated. A total of 54 Gram-negative isolates, belonging to diverse species, were collected from wastewater sample and river sample. All isolates were classified as MDR, exhibiting resistance to at least one agent from more than three different antibiotic classes. Based on species identification and susceptibility profiles, 27 isolates (19 from wastewater and 8 from river-water) were selected to be further characterized by whole-genome sequencing (WGS). Analysis of WGS data, revealed the presence of different STs, even in isolates belonging to the same bacterial species. Additionally, WGS data showed that carbapenemase-encoding genes were identified in the majority of isolates. PlasmidFinder identified a huge variety of plasmid replicons among the isolates studied. In conclusion, both hospital wastewater and river water contained isolates carrying clinically relevant resistance determinants, such as carbapenemase-encoding genes. The presence of these pathogenic bacteria in the river poses a significant public health concern. Although we could not identify the origin of MDR bacteria in the river sample, these findings highlight the growing threat of antimicrobial resistance in the environment and underscore the urgent need for improved treatment methods and stricter surveillance to control its spread. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3863 Familial cancers associated with cancers of the breast, prostate, colorectum and lung in Sweden Zitrický, František; Sundquist, Kristina; Sundquist, Jan; Hemminki, Akseli; Försti, Asta; Hemminki, Kari Jussi Available epidemiological evidence shows that many cancers share familial risks, and this is increasingly confirmed by data on shared pathogenic germline gene variants between cancers. We decided to harness the world's largest resource on familial cancer to assess discordant familial risks for female breast (BC), prostate (PC), colorectal (CRC) and lung (LC) cancers with any of 22 different cancers in first-degree relatives (proband cancers). Familial relative risk was calculated as standardized incidence ratio (SIR) when either one proband or 2 or more (2+) probands were found in a family to distinguish low- and high-risk associations. Discordant familial associations of BC were significant for 15 1-proband and 6 2+ proband cancers. For PC the numbers were 10 and 4, for CRC they were 9 and 3 and for LC they were 14 and 5. The results with large case numbers showed that BC, CRC and LC associated with each other but the familial association between PC and LC was negative. Many novel associations with possible genetic causes were found, including lobular BC with stomach cancer, PC with kidney cancer, CRC with squamous cell skin, brain and thyroid cancers, and LC with gallbladder and endocrine tumors, the most common of which were parathyroid adenomas. Also, LC associations with esophageal and cervical cancers were unlikely to be due to smoking alone and require additional explanations. In conclusion, 2/3 of discordant associations could suggest low-risk genetic and environmental causation and 1/3 high-risk genetic causation, both waiting for experimental proof. 2026-01-01T00:00:00Z