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Article

Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer

  • Authors:
    • Semra Demokan
    • Alice Y. Chuang
    • Kavita M. Pattani
    • David Sidransky
    • Wayne Koch
    • Joseph A. Califano
  • View Affiliations / Copyright

    Affiliations: Department of Basic Oncology, Oncology Institute, Istanbul University, Capa, Istanbul 34093, Turkey, Department of Dermatology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
  • Pages: 1014-1020
    |
    Published online on: December 16, 2013
       https://doi.org/10.3892/or.2013.2927
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Abstract

Methylation of CpG islands in the promoter region of genes acts as a significant mechanism of epigenetic gene silencing in head and neck cancer. In the present study, we assessed the association of epigenetic alterations of a panel of 12 genes [nucleolar protein 4 (NOL4), iroquois homeobox 1 (IRX1), SLC5A8, LRRC3B, FUSSEL18, EBF3, GBX2, HMX2, SEPT9, ALX3, SOCS3 and LHX6] with head and neck squamous cell carcinoma (HNSCC) via a candidate gene approach. After the initial screening of methylated CpG islands on the promoter regions by bisulfite sequencing using salivary rinse samples, only two genes had methylated CpG dinucleotides on their promoter regions in tumor samples and absence of methylated CpGs were found in normal salivary rinse samples after bisulfite modification and bisulfite sequencing. We then performed real-time quantitative methylation-specific PCR (QMSP) on 16 salivary rinse and 14 normal mucosal samples from healthy subjects and 33 HNSCC tumor samples for the two genes selected. After validation with QMSP, one gene, NOL4, was highly methylated (91%) in tumor samples and unmethylated in normal salivary rinses and minimally methylated in normal mucosal samples demonstrating cancer-specific methylation in HNSCC tissues. Although the IRX1 gene was observed as methylated in normal mucosal and salivary rinse samples, the methylation values of these normal samples were very low (<10%). In conclusion, we identified NOL4 as a highly specific promoter methylated gene associated with HNSCC. IRX1 may have potential as a biomarker for HNSCC and should be assessed in a larger cohort.
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Copy and paste a formatted citation
Spandidos Publications style
Demokan S, Chuang AY, Pattani KM, Sidransky D, Koch W and Califano JA: Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer. Oncol Rep 31: 1014-1020, 2014.
APA
Demokan, S., Chuang, A.Y., Pattani, K.M., Sidransky, D., Koch, W., & Califano, J.A. (2014). Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer. Oncology Reports, 31, 1014-1020. https://doi.org/10.3892/or.2013.2927
MLA
Demokan, S., Chuang, A. Y., Pattani, K. M., Sidransky, D., Koch, W., Califano, J. A."Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer". Oncology Reports 31.2 (2014): 1014-1020.
Chicago
Demokan, S., Chuang, A. Y., Pattani, K. M., Sidransky, D., Koch, W., Califano, J. A."Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer". Oncology Reports 31, no. 2 (2014): 1014-1020. https://doi.org/10.3892/or.2013.2927
Copy and paste a formatted citation
x
Spandidos Publications style
Demokan S, Chuang AY, Pattani KM, Sidransky D, Koch W and Califano JA: Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer. Oncol Rep 31: 1014-1020, 2014.
APA
Demokan, S., Chuang, A.Y., Pattani, K.M., Sidransky, D., Koch, W., & Califano, J.A. (2014). Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer. Oncology Reports, 31, 1014-1020. https://doi.org/10.3892/or.2013.2927
MLA
Demokan, S., Chuang, A. Y., Pattani, K. M., Sidransky, D., Koch, W., Califano, J. A."Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer". Oncology Reports 31.2 (2014): 1014-1020.
Chicago
Demokan, S., Chuang, A. Y., Pattani, K. M., Sidransky, D., Koch, W., Califano, J. A."Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer". Oncology Reports 31, no. 2 (2014): 1014-1020. https://doi.org/10.3892/or.2013.2927
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