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Identification of FOXM1‐induced epigenetic markers for head and neck squamous cell carcinomas
Author(s) -
Hwang Sungjae,
Mahadevan Swarna,
Qadir Fatima,
Hutchison Iain L.,
Costea Daniela Elena,
Neppelberg Evelyn,
Liavaag Per Gunnar,
Waseem Ahmad,
Teh MuyTeck
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28354
Subject(s) - epigenetics , dna methylation , cancer research , reprogramming , cancer , head and neck squamous cell carcinoma , foxm1 , methylation , biology , medicine , head and neck cancer , genetics , gene expression , gene , cell cycle
BACKGROUND 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 FOXM1 has been implicated in all major forms of human cancer. METHODS We have recently shown that aberrant upregulation of FOXM1 orchestrated a DNA methylation signature that mimics the cancer methylome landscape, from which we have identified a number of FOXM1 ‐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. RESULTS Here, we investigated 8 FOXM1 ‐induced differentially methylated genes, SPCS1, FLNA, CHPF, GLT8D1, C6orf136, MGAT1, NDUFA10, and PAFAH1B3, using human head and neck tissue specimens donated by 2 geographically independent patient cohorts from Norway and the United Kingdom. Two genes ( GLT8D1 and C6orf136 ) 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 GLT8D1 and C6orf136 were hypo‐ and hypermethylated, respectively, in HNSCC tissues. CONCLUSIONS 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. Cancer 2013;119:4249–4258 . © 2013 American Cancer Society .