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- W2890645189 abstract "e21077 Background: Cutaneous melanomas display considerably higher mutational load compared to other solid tumors, mainly due to DNA damage and absent/defective repair. Chromatin organization plays an important role in these processes, with open chromatin conferring a higher sensitivity to DNA damage. BORIS is an epigenetic modifier that is correlated with open chromatin and is abnormally expressed in primary and metastatic melanoma. Here we set out to obtain a better understanding of BORIS’s role in chromatin organization and DNA damage in melanoma. Methods: A panel of melanoma cell lines was selected and BORIS mRNA expression was determined using qPCR. Cellular localization of BORIS was assessed by immunofluorescence. Ectopic BORIS expression was established exploiting a doxycycline inducible expression vector and proliferation was assessed using crystal violet and Hoechst staining. DNA damage was induced by exposure to 60 J/m 2 UVC followed by apoptosis and cell cycle analysis using flow cytometry. Results: We confirmed aberrant BORIS expression in 61% of our melanoma cell line panel and observed nuclear BORIS localization in areas of low chromatin density. Forced expression of BORIS in BORIS low/intermediate cell lines resulted in a significant reduction in cell growth and increased cell death. Interestingly, BORIS overexpressing cells exposed to UV irradiation displayed a higher degree of cell cycle alterations and increased level of apoptosis compared to BORIS low/intermediate cells. Conclusions: Our results demonstrate that BORIS is increased in melanoma, localized in areas of open chromatin, and increased sensitivity to UV-induced DNA damage. Taken together, this indicates a role for BORIS in directing the chromatin state into a more open conformation, allowing increased sensitivity to DNA damage. Currently, we are analyzing DNA damage in BORIS overexpressing cells and are further investigating BORIS’s role in directing chromatin state by exploiting ATAC-seq and ChIP-seq for various epigenetic marks." @default.
- W2890645189 created "2018-09-27" @default.
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- W2890645189 date "2017-05-20" @default.
- W2890645189 modified "2023-09-23" @default.
- W2890645189 title "Impact of the epigenetic modulator BORIS on sensitivity of melanoma cells to UV-induced DNA damage." @default.
- W2890645189 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e21077" @default.
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