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DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

K. Tomasova, A. Cumova, K. Seborova, J. Horak, K. Koucka, L. Vodickova, R. Vaclavikova, P. Vodicka,

. 2020 ; 12 (7) : . [pub] 20200628

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/bmc20022056

Grantová podpora
19-10543S Grantová Agentura České Republiky
NV-18/03/00199 Agentura Pro Zdravotnický Výzkum České Republiky
LTC19020 Ministerstvo Školství, Mládeže a Tělovýchovy
(NPU I) Nr. LO1503 Ministerstvo Školství, Mládeže a Tělovýchovy
PROGRES Q 28 Univerzita Karlova v Praze
UNCE/MED/006 Univerzita Karlova v Praze

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.

Citace poskytuje Crossref.org

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$a Tomasova, Kristyna $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic. Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 32300 Pilsen, Czech Republic.
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$a 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.
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$a Cumova, Andrea $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic. First Faculty of Medicine, Charles University, Institute of Biology and Medical Genetics, Albertov 4, 12800 Prague, Czech Republic.
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$a Horak, Josef $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic. Third Faculty of Medicine, Charles University, Ruska 87, 10000 Prague, Czech Republic.
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$a Koucka, Kamila $u Toxicogenomics Unit, National Institute of Public Health, Srobarova 48, 10042 Prague, Czech Republic. Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 32300 Pilsen, Czech Republic.
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$a Vodickova, Ludmila $u Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic. Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 76, 32300 Pilsen, Czech Republic. First Faculty of Medicine, Charles University, Institute of Biology and Medical Genetics, Albertov 4, 12800 Prague, Czech Republic.
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