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The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
Although much effort is made to prevent risks arising from food, food-borne diseases are an ever-present threat to the consumers’ health. The consumption of fresh food that is contaminated with pathogens like fungi, viruses or bacteria can cause food poisoning that leads to severe health damages or even death. The outbreak of Shiga Toxin-producing enterohemorrhagic E. coli (EHEC) in Germany and neighbouring countries in 2011 has shown this dramatically. Nearly 4.000 people were reported of being affected and more than 50 people died during the so called EHEC-crisis. As a result the consumers’ trust in the safety of fruits and vegetables decreased sharply.
Agricultural activities within city boundaries have a long history in both developed and developing countries. In this paper, a broad approach to Urban AgriCulture (UAC) is used, one that includes the production of crops in urban and peri-urban areas and ranges in developed countries from allotment gardens over community gardens to semi-entrepreneurial self-harvest farms and fully commercialized agriculture. With an empirical case study on UAC Initiatives in the Bonn/Rhein-Sieg region this work fills a gap since the lack of comprehensive and comparative studies on urban agriculture (UA) currently makes it difficult for researchers to identify the benefits of UA activities.