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Disease Markers
Volume 2014, Article ID 260549, 8 pages
http://dx.doi.org/10.1155/2014/260549
Review Article

p16INK4A and p14ARF Gene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review

1Department of Pathology, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
2Department of Radiation Oncology, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands
3Department of Otorhinolaryngology, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands

Received 26 November 2013; Accepted 17 March 2014; Published 7 April 2014

Academic Editor: Silvia Persichilli

Copyright © 2014 A. Al-Kaabi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteins and and to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status of is definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival.