Identification of FOXM1-induced epigenetic markers for head and neck squamous cell carcinomas

Authors

  • Sungjae Hwang BSc, MBBS,

    1. Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom
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  • Swarna Mahadevan BDS, MSc,

    1. Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom
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  • Fatima Qadir BDS, MSc,

    1. Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom
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  • Iain L. Hutchison MB, BDS, FFDRCSI, FRCS,

    1. Department of Oral & Maxillofacial Surgery, Barts & The London NHS Trust, London, England, United Kingdom
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  • Daniela Elena Costea DDS, PhD,

    1. The Gade Laboratory of Pathology, Department of Clinical Medicine, University of Bergen, and Department of Pathology, Haukeland University Hospital, Bergen, Norway
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  • Evelyn Neppelberg DDS, PhD,

    1. Department of Oral Surgery, Haukeland University Hospital, and Institute of Clinical Dentistry, University of Bergen, Bergen, Norway
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  • Per Gunnar Liavaag MD, PhD,

    1. Department of Otolaryngology and Head & Neck Surgery, Head and Neck Clinic, Haukeland University Hospital, Bergen, Norway
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  • Ahmad Waseem BSc, PhD,

    1. Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom
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  • Muy-Teck Teh BSc, PhD

    Corresponding author
    1. Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, England, United Kingdom
    • Corresponding author: Dr. Muy-Teck Teh, BSc, PhD, Centre for Clinical and Diagnostic Oral Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, The Blizzard Building, 4, Newark Street, London E1 2AT, United Kingdom; Fax: (011) 44 20 7882 7137; m.t.teh@qmul.ac.uk

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Abstract

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.

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