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• W2915057732 endingPage "197" @default.
• W2915057732 startingPage "185" @default.
• W2915057732 abstract "The POTE gene family consists of 14 homologous genes localized to autosomal pericentromeres, and a sub-set of POTEs are cancer-testis antigen (CTA) genes. POTEs are over-expressed in epithelial ovarian cancer (EOC), including the high-grade serous subtype (HGSC), and expression of individual POTEs correlates with chemoresistance and reduced survival in HGSC. The mechanisms driving POTE overexpression in EOC and other cancers is unknown. Here, we investigated the role of epigenetics in regulating POTE expression, with a focus on DNA hypomethylation. Consistent with their pericentromeric localization, Pan-POTE expression in EOC correlated with expression of the pericentromeric repeat NBL2, which was not the case for non-pericentromeric CTAs. POTE genomic regions contain LINE-1 (L1) sequences, and Pan-POTE expression correlated with both global and POTE-specific L1 hypomethylation in EOC. Analysis of individual POTEs using RNA-seq and DNA methylome data from fallopian tube epithelia (FTE) and HGSC revealed that POTEs C, E, and F have increased expression in HGSC in conjunction with DNA hypomethylation at 5' promoter or enhancer regions. Moreover, POTEs C/E/F showed additional increased expression in recurrent HGSC in conjunction with 5' hypomethylation, using patient-matched samples. Experiments using decitabine treatment and DNMT knockout cell lines verified a functional contribution of DNA methylation to POTE repression, and epigenetic drug combinations targeting histone deacetylases (HDACs) and histone methyltransferases (HMTs) in combination with decitabine further increased POTE expression. In summary, several alterations of the cancer epigenome, including pericentromeric activation, global and locus-specific L1 hypomethylation, and locus-specific 5' CpG hypomethylation, converge to promote POTE expression in ovarian cancer." @default.
• W2915057732 created "2019-02-21" @default.
• W2915057732 creator A5009400324 @default.
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• W2915057732 creator A5088271731 @default.
• W2915057732 date "2019-02-01" @default.
• W2915057732 modified "2023-09-24" @default.
• W2915057732 title "Epigenetic activation of <i>POTE</i> genes in ovarian cancer" @default.
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• W2915057732 doi "https://doi.org/10.1080/15592294.2019.1581590" @default.
• W2915057732 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6557602" @default.
• W2915057732 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30764732" @default.
• W2915057732 hasPublicationYear "2019" @default.
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