Identification of FOXM1‐induced epigenetic markers for head and neck squamous cell carcinomas. Issue 24 (1st October 2013)

• Record Type: Journal Article
• Authors: Hwang, Sungjae; Mahadevan, Swarna; Qadir, Fatima; Hutchison, Iain L.; Costea, Daniela Elena; Neppelberg, Evelyn; Liavaag, Per Gunnar; Waseem, Ahmad; Teh, Muy‐Teck
• Is Part Of: Cancer. Volume 119:Issue 24(2013)
• Page Start: 4249
• Page End: 4258
• Publication Date: 2013-10-01
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.28354
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr28354-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Epigenetic reprogramming of the methylome has been implicated in all stages of cancer evolution. It is now well accepted that cancer cells exploit epigenetic reprogramming, a mechanism that regulates stem/progenitor cell renewal and differentiation, to promote cancer initiation and progression. The oncogene <italic>FOXM1</italic> has been implicated in all major forms of human cancer.</p> </sec> <sec id="cncr28354-sec-0002" sec-type="section"> <title>METHODS</title> <p>We have recently shown that aberrant upregulation of <italic>FOXM1</italic> orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a number of <italic>FOXM1</italic>‐induced epigenetic markers. Differential promoter methylation and gene expression in clinical specimens were measured using commercially available bisulfite conversion kits and absolute quantitative PCR, respectively.</p> </sec> <sec id="cncr28354-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Here, we investigated 8 <italic>FOXM1</italic>‐induced differentially methylated genes, <italic>SPCS1, FLNA, CHPF, </italic><italic>GLT8D1, C6orf136, MGAT1, NDUFA10, </italic> and <italic>PAFAH1B3, </italic> using human head and neck tissue specimens donated by 2 geographically independent patient cohorts from Norway and the United Kingdom. Two genes (<italic>GLT8D1</italic> and <italic>C6orf136</italic>) were found to be differentially expressed in head and neck squamous cell carcinomas (HNSCCs). Using methylation‐specific quantitative PCR, we confirmed that the promoters of <italic>GLT8D1</italic> and <italic>C6orf136</italic> were hypo‐ and hypermethylated, respectively, in HNSCC tissues.</p> </sec> <sec id="cncr28354-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Given that epigenetic change precedes gene expression, methylation status of candidate genes identified from this study may represent a signature of premalignancy, rendering them potentially useful predictive biomarkers for precancer screening and/or therapeutic targets for cancer prevention. <bold><italic>Cancer</italic> 2013;119:4249–4258</bold>. © <italic>2013 American Cancer Society</italic>.</p> </sec> </abstract>