Biological significance of 5-hydroxymethylcytosine in oral epithelial dysplasia and oral squamous cell carcinoma

Publication date: January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 125, Issue 1
Author(s): Maria Carolina Cuevas-Nunez, Camilla Borges F. Gomes, Sook-Bin Woo, Matthew R. Ramsey, Xiaoxin L. Chen, Shuyun Xu, Ting Xu, Qian Zhan, George F. Murphy, Christine G. Lian
ObjectivesThe aim of this study was to determine the levels of 5-hydroxylmethylcytosine (5-hmC) in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) compared with those in benign, reactive inflammatory lesions and to explore whether DNA hydroxymethylation may serve as a novel biomarker for early diagnosis and prognosis of OSCC.Study DesignThe study included normal mucosa from uninvolved margins of 9 fibromas, 10 oral lichen planus, 15 OED, and 23 OSCC. Cultured human keratinocyte lines from benign oral mucosa, OED, and OSCC, as well as a murine model in which OSCC was induced with 4-nitroquinoline-1-oxide, were also evaluated.ResultsProgressive loss of 5-hmC from benign oral mucosal lesions to OED and OSCC was documented in patient samples. Decreased levels in 5-hmC that typify OED and OSCC were also detectable in human cell lines. Moreover, we characterized similar alterations in 5-hmC in an animal model of OED/OSCC.ConclusionsThis study demonstrated that 5-hmC distinguishes OED and OSCC from benign lesions with high sensitivity and specificity. Consequently, loss of 5-hmC may be useful for the diagnosis of OED with potential implications for therapy of OSCC.



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