Pre-neoplastic epigenetic disruption of transcriptional enhancers in chronic inflammation
| Autor: | Ken Kron, Daniel D. De Carvalho, Mathieu Lupien, Sergio Roberto Peres Line, Aline Cristiane Planello, Rajat Singhania, Ana Paula de Souza, David Roulois, Swneke D. Bailey |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Inflammation Biology oral cavity squamous cell carcinoma Epigenesis Genetic 03 medical and health sciences 0302 clinical medicine medicine Humans Epigenetics Enhancer Mouth neoplasm Genetics DNA methylation Squamous Cell Carcinoma of Head and Neck chronic periodontitis Epigenome Methylation 3. Good health Chromatin stomatognathic diseases 030104 developmental biology Enhancer Elements Genetic Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis Cancer research Carcinoma Squamous Cell enhancers Female Mouth Neoplasms medicine.symptom Precancerous Conditions Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Chronic periodontitis (CP) is a chronic inflammatory disease independently associated with higher incidence of oral cavity squamous cell carcinoma (OSCC). However, the molecular mechanism responsible for this increased incidence is unknown. Here we profiled the DNA methylome of CP patients and healthy controls and compared to a large set of OSCC samples from TCGA. We observed a significant overlap between the altered DNA methylation patterns in CP and in OSCC, suggesting an emergence of a pre-neoplastic epigenome in CP. Remarkably, the hypermethylated CpGs in CP were significantly enriched for enhancer elements. This aberrant enhancer methylation is functional and able to disrupt enhancer activity by preventing the binding of chromatin looping factors. This study provides new insights on the molecular mechanisms linking chronic inflammation and tumor predisposition, highlighting the role of epigenetic disruption of transcriptional enhancers. |
| Databáze: | OpenAIRE |
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