Abstract 666: Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 666
• Main Authors: Demokan, Semra, Chuang, Alice Y., Pattani, Kavita M., Sidransky, David, Koch, Wayne, Califano, Joseph A.
• Format: Journal Article
• Language: English
• Published: 15-04-2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-666

Purpose: 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 this study, we assessed the utility of epigenetic alterations of a panel of twelve genes (NOL4, IRX1, SLC5A8, LRRC3B, FUSSEL18, EBF3, GBX2, HMX2, SEPT9, ALX3, SOCS3, LHX6) previously reported.
Experimental Design: In this study we investigated methylation of the 12 gene promoters 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 quantitative methylation specific PCR (Q-MSP) on 16 salivary rinse and 14 normal mucosal samples from healthy people and 33 HNSCC tumor samples for two genes selected.
Results: After validation with QMSP, one gene, nucleolar protein 4 (NOL4), was highly methylated (91%) in tumor samples and unmethylated in normal salivary rinse samples and minimally methylated in normal mucosal samples demonstrating cancer specific methylation in HNSCC tissues. Although iroquois homeobox 1 (IRX1) gene was observed as methylated in normal mucosal and salivary rinse samples, indeed, the methylation values of these normal samples were very low (less than 10%).
Conclusions: We identified NOL4, as a highly specific promoter methylated gene was associated with HNSCC. IRX1 which may have a potential as a biomarker for HNSCC and should also be assessed in a larger cohort.
Citation Format: Semra Demokan, Alice Y. Chuang, Kavita M. Pattani, David Sidransky, Wayne Koch, Joseph A. Califano. Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 666. doi:10.1158/1538-7445.AM2013-666