DNA methylation markers for oral pre-cancer progression: A critical review. (February 2016)

• Record Type: Journal Article
• Authors: Shridhar, Krithiga; Walia, Gagandeep Kaur; Aggarwal, Aastha; Gulati, Smriti; Geetha, A.V.; Prabhakaran, Dorairaj; Dhillon, Preet K.; Rajaraman, Preetha
• Is Part Of: Oral oncology. Volume 53(2016:Feb.)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-02
• Subjects: DNA methylation -- Oral pre-cancer -- Bio-marker -- Epigenetics -- Leukoplakia -- Oral sub-mucous fibrosis -- Promoter regions -- CpG sites -- Tumour suppressor genes -- Diagnostic marker; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2015.11.012
• Languages: English
• ISSNs: 1368-8375

Abstract

Graphical abstract: Highlights: We critically reviewed DNA methylation patterns for oral pre-cancer progression. Suggestive signals included hyper-methylated loci in p16, p14, MGMT and DAPK. Large epigenome-wide explorations are needed to validate these markers and to identify new risk loci and biological pathways of disease progression. Summary: Although oral cancers are generally preceded by a well-established pre-cancerous stage, there is a lack of well-defined clinical and morphological criteria to detect and signal progression from pre-cancer to malignant tumours. We conducted a critical review to summarize the evidence regarding aberrant DNA methylation patterns as a potential diagnostic biomarker predicting progression. We identified all relevant human studies published in English prior to 30th April 2015 that examined DNA methylation (%) in oral pre-cancer by searching PubMed, Web-of-Science and Embase databases using combined key-searches. Twenty-one studies (18-cross-sectional; 3-longitudinal) were eligible for inclusion in the review, with sample sizes ranging from 4 to 156 affected cases. Eligible studies examined promoter region hyper-methylation of tumour suppressor genes in pathways including cell-cycle-control ( n = 15), DNA-repair ( n = 7), cell-cycle-signalling ( n = 4) and apoptosis ( n = 3). Hyper-methylated loci reported in three or more studies included p16, p14, MGMT and DAPK. Two longitudinal studies reported greater p16 hyper-methylation in pre-cancerous lesions transformed to malignancy compared to lesions that regressed (57–63.6% versus 8–32.1%; p < 0.01). The one study that explored epigenome-wide methylation patterns reported three novel hyper-methylated loci ( TRHDE ; ZNF454 ; KCNAB3 ). The majority of reviewed studies were small, cross-sectional studies with poorly defined control groups and lacking validation. Whilst limitations in sample size and study design preclude definitive conclusions, current evidence suggests a potential utility of DNA methylation patterns as a diagnostic biomarker for oral pre-cancer progression. Robust studies such as large epigenome-wide methylation explorations of oral pre-cancer with longitudinal tracking are needed to validate the currently reported signals and identify new risk-loci and the biological pathways of disease progression.