Frequent hypermethylation of WNT pathway genes in laryngeal squamous cell carcinomas. (25th April 2014)

• Record Type: Journal Article
• Authors: Paluszczak, Jarosław; Hemmerling, Dawid; Kostrzewska‐Poczekaj, Magdalena; Jarmuż‐Szymczak, Małgorzata; Grenman, Reidar; Wierzbicka, Małgorzata; Baer‐Dubowska, Wanda
• Is Part Of: Journal of oral pathology & medicine. Volume 43:Number 9(2014:Oct.)
• Page Start: 652
• Page End: 657
• Publication Date: 2014-04-25
• Subjects: Dentistry -- Periodicals; Teeth -- Diseases -- Periodicals; 617
• DOI: 10.1111/jop.12178
• Languages: English
• ISSNs: 0904-2512

Abstract

<abstract abstract-type="main" id="jop12178-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jop12178-sec-0001" sec-type="section"> <title>Background</title> <p>Aberrations in the function of the WNT signaling pathway have been recently implicated in the pathogenesis of head and neck cancer, and the hypermethylation of several WNT cascade inhibitors were shown to be useful in disease prognosis. However, the extent of deregulation of WNT pathway by DNA hypermethylation has not been studied in detail in laryngeal cancer so far. The aim of this study was to establish the frequency of methylation of WNT pathway negative regulators in laryngeal squamous cell carcinomas and evaluate its prognostic significance.</p> </sec> <sec id="jop12178-sec-0002" sec-type="section"> <title>Methods</title> <p>Twenty‐six laryngeal squamous cell carcinoma cell lines and samples obtained from twenty‐eight primary laryngeal carcinoma patients were analyzed. The methylation status of <italic>DKK1, LKB1, PPP2R2B, RUNX3, SFRP1, SFRP2, </italic> and <italic>WIF‐1</italic> was assessed using the methylation‐specific polymerase chain reaction.</p> </sec> <sec id="jop12178-sec-0003" sec-type="section"> <title>Results</title> <p>Frequent hypermethylation of <italic>DKK1, PPP2R2B, SFRP1, SFRP2, </italic> and <italic>WIF‐1</italic> was detected, and a high methylation index was usually observed. Half of the cell lines analyzed and seventy percent of primary laryngeal carcinoma cases were characterized by the methylation of at least four genes. The hypermethylation of <italic>PPP2R2B</italic> or <italic>WIF‐1</italic> was associated with longer survival in laryngeal carcinoma cell lines. Moreover, the concurrent methylation of <italic>PPP2R2B</italic> and <italic>SFRP1</italic> differentiated primary from recurrent laryngeal carcinoma cell lines.</p> </sec> <sec id="jop12178-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Frequent hypermethylation of WNT pathway negative regulators is observed in laryngeal squamous cell carcinomas. The possible prognostic significance of the methylation of <italic>DKK1, PPP2R2B, </italic> and <italic>SFRP1</italic> needs to be evaluated in further prospective studies.</p> </sec> </abstract>