title: Pre-neoplastic epigenetic disruption of transcriptional enhancers in chronic inflammation.
abstract: 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.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Morphology, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil.
authors.forename: Aline C
authors.initials: AC
authors.lastname: Planello
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Rajat
authors.initials: R
authors.lastname: Singhania
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Kron
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: Swneke D
authors.initials: SD
authors.lastname: Bailey
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Roulois
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lupien
authors.affiliation: Department of Morphology, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil.
authors.forename: Sérgio R Peres
authors.initials: SR
authors.lastname: Line
authors.affiliation: Department of Morphology, Piracicaba Dental School, University of Campinas, Piracicaba, SP, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de Souza
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: De Carvalho
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D055113:Chronic Periodontitis / Q000235:genetics*; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: DNA methylation; chronic periodontitis; enhancers; oral cavity squamous cell carcinoma