There is ample evidence for the essential involvement of DNA repair and DNA damage response in the onset of solid malignancies, including ovarian cancer. Indeed, highpenetrance germline mutations in DNA repair genes are important players in familial cancers: BRCA1, BRCA2 mutations or mismatch repair, and polymerase deficiency in colorectal, breast, and ovarian cancers. Recently, some molecular hallmarks (e.g., TP53, KRAS, BRAF, RAD51C/D or PTEN mutations) of ovarian carcinomas were identified. The manuscript overviews the role of DNA repair machinery in ovarian cancer, its risk, prognosis, and therapy outcome. We have attempted to expose molecular hallmarks of ovarian cancer with a focus on DNA repair system and scrutinized genetic, epigenetic, functional, and protein alterations in individual DNA repair pathways (homologous recombination, non-homologous end-joining, DNA mismatch repair, base- and nucleotide-excision repair, and direct repair). We suggest that lack of knowledge particularly in non-homologous end joining repair pathway and the interplay between DNA repair pathways needs to be confronted. The most important genes of the DNA repair system are emphasized and their targeting in ovarian cancer will deserve further attention. The function of those genes, as well as the functional status of the entire DNA repair pathways, should be investigated in detail in the near future.

1st Faculty of Medicine Charles University Institute of Biology and Medical Genetics Albertov 4 12800 Prague Czech Republic

3rd Faculty of Medicine Charles University Ruska 87 10000 Prague Czech Republic

Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 76 32300 Pilsen Czech Republic

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Videnska 1083 14220 Prague Czech Republic

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 76 32300 Pilsen Czech Republic

Toxicogenomics Unit National Institute of Public Health Srobarova 48 10042 Prague Czech Republic

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Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy

Whole-exome sequencing of epithelial ovarian carcinomas differing in resistance to platinum therapy

Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers