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

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

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),...

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Main Authors: DEMOKAN, SEMRA, CHUANG, ALICE Y., PATTANI, KAVITA M., SIDRANSKY, DAVID, KOCH, WAYNE, CALIFANO, JOSEPH A.
Format: Online
Language:English
Published: D.A. Spandidos 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896520/
id pubmed-3896520
recordtype oai_dc
spelling pubmed-38965202014-01-21 Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer DEMOKAN, SEMRA CHUANG, ALICE Y. PATTANI, KAVITA M. SIDRANSKY, DAVID KOCH, WAYNE CALIFANO, JOSEPH A. Articles 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. D.A. Spandidos 2014-02 2013-12-16 /pmc/articles/PMC3896520/ /pubmed/24337411 http://dx.doi.org/10.3892/or.2013.2927 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author DEMOKAN, SEMRA
CHUANG, ALICE Y.
PATTANI, KAVITA M.
SIDRANSKY, DAVID
KOCH, WAYNE
CALIFANO, JOSEPH A.
spellingShingle DEMOKAN, SEMRA
CHUANG, ALICE Y.
PATTANI, KAVITA M.
SIDRANSKY, DAVID
KOCH, WAYNE
CALIFANO, JOSEPH A.
Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
author_facet DEMOKAN, SEMRA
CHUANG, ALICE Y.
PATTANI, KAVITA M.
SIDRANSKY, DAVID
KOCH, WAYNE
CALIFANO, JOSEPH A.
author_sort DEMOKAN, SEMRA
title Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
title_short Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
title_full Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
title_fullStr Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
title_full_unstemmed Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
title_sort validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer
description 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.
publisher D.A. Spandidos
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896520/
_version_ 1612049124898635776

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