Úloha telomer / DNA reparací v solidních tumorech

Tomášová, Kristýna

Loss of telomere function and unrepaired DNA damage contribute to chromosome integrity disruption and genomic instability development, which can initiate malignant transformation of the cells. This dissertation focused on telomeres and their maintenance and regulation mechanisms in sporadic colorectal, breast, and ovarian tumors. In colorectal cancer (CRC), a place was also dedicated to research on base excision repair glycosylases. The findings of the Thesis are elaborated in detail in seven attached Manuscripts. The main results of each of the articles are as follows: I) Mitochondrial DNA copy number changes and telomere length (TL) shortening already occur in precancerous lesions of CRC, but in early carcinomas, the association between their mitochondrial DNA content and TL diminishes; II) TL of leukocytes in peripheral blood of patients with CRC can be affected by postoperative cytostatic treatment based on 5-fluorouracil; III) CRC liver metastases maintain the same TL as primary tumors. In addition, neoadjuvant treatment with (chemo)radiotherapy applied to patients with rectal cancer probably causes telomere shortening in the primary tumor and the surrounding rectal cells in addition to DNA damage; IV) TL of ovarian cancer cells can be influenced by epigenetic regulations and expressions of...

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