Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma.
Genome Med
; 13(1): 130, 2021 08 16.
Article
em En
| MEDLINE
| ID: mdl-34399838
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with limited treatment possibilities. Merkel cell tumors display with neuroendocrine features and Merkel cell polyomavirus (MCPyV) infection in the majority (80%) of patients. Although loss of histone H3 lysine 27 trimethylation (H3K27me3) has been shown during MCC tumorigenesis, epigenetic dysregulation has largely been overlooked. METHODS: We conducted global DNA methylation profiling of clinically annotated MCC primary tumors, metastatic skin tumors, metastatic lymph node tumors, paired normal tissues, and two human MCC cell lines using the Illumina Infinium EPIC DNA methylation BeadArray platform. RESULTS: Significant differential DNA methylation patterns across the genome are revealed between the four tissue types, as well as based on MCPyV status. Furthermore, 964 genes directly regulated by promoter or gene body DNA methylation were identified with high enrichment in neuro-related pathways. Finally, our findings suggest that loss of H3K27me3 occupancy in MCC is attributed to KDM6B and EZHIP overexpression as a consequence of promoter DNA hypomethylation. CONCLUSIONS: We have demonstrated specific DNA methylation patterns for primary MCC tumors, metastatic MCCs, and adjacent-normal tissues. We have also identified DNA methylation markers that not only show potential diagnostic or prognostic utility in MCC management, but also correlate with MCC tumorigenesis, MCPyV expression, neuroendocrine features, and H3K27me3 status. The identification of DNA methylation alterations in MCC supports the need for further studies to understand the clinical implications of epigenetic dysregulation and potential therapeutic targets in MCC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Célula de Merkel
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Regulação Neoplásica da Expressão Gênica
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Metilação de DNA
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Transcriptoma
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Genome Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos