Maria Carolina Cuevas-Nunez1, Camilla Borges F Gomes2, Sook-Bin Woo3, Matthew R Ramsey4, Xiaoxin L Chen5, Shuyun Xu2, Ting Xu2, Qian Zhan2, George F Murphy2, Christine G Lian6. 1. Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Oral Medicine and Dentistry, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, MA, USA. 2. Department of Oral Medicine and Dentistry, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, MA, USA. 3. Department of Oral Medicine and Dentistry, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, MA, USA; StrataDx, Lexington, MA, USA. 4. Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 5. Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, USA. 6. Department of Oral Medicine and Dentistry, Brigham and Women's Hospital, Harvard School of Dental Medicine, Boston, MA, USA. Electronic address: cglian@bwh.harvard.edu.
Abstract
OBJECTIVES: The 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 DESIGN: The 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. RESULTS: Progressive 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. CONCLUSIONS: This 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.
OBJECTIVES: The 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 DESIGN: The 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. RESULTS: Progressive 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. CONCLUSIONS: This 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.