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National Repository of Grey Literature 1 records found  Search took 0.01 seconds. 
Tracing intestinal tumorigenesis driven by BRAF V600E oncogene
 Herrmannová, Terezie ; Hrčkulák, Dušan (advisor) ; Vomastek, Tomáš (referee)
Colorectal carcinoma is one of the most commonly diagnosed tumor diseases worldwide and is the cause of more than nine percent of deaths due to neoplasia. Colorectal cancer develops through different ways and one of them is the so-called serrated pathway, which is characterized by the presence of the BRAF V600E oncogenic mutation. Tumors arising through serrated pathway do not respond to classical therapy, and therefore are currently being studied at the molecular level. The oncogenic variant of the BRAF kinase activates MAPK signaling and is considered to be the main cause of serrated intestinal tumor formation. However, the mere presence of this oncogene is not sufficient for tumor development that requires further changes within the genome of the cell. In this thesis, we try to clarify what effect the BRAF V600E mutation has on the cells of the intestinal epithelium. In addition, we try to identify a possible cooperation between BRAF gene mutation and disruption of p53 and Wnt signaling, whose components are also frequently mutated in colorectal cancer. As a model for studying the processes associated with BRAF V600E activation, we use a mouse strain with conditional expression of a mutant variant of the Braf gene. We isolate intestinal organoids from these mice and subsequently perform in vitro...
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