Epigenetic and Genetic Alterations of the &lt;i&gt;EDNRB&lt;/i&gt; Gene in Nasopharyngeal Carcinoma

Zhou, Liang; Feng, Xiangling; Shan, Wenjiao; Zhou, Wen; Liu, Weidong; Wang, Lei; Zhu, Bin; Yi, Hongmei; Yao, Kangde; Ren, Chao

doi:10.1159/000113146

Cited by 20 publications

(10 citation statements)

References 56 publications

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“…The promoter methylation status of EDNRB gene was studied previously in bladder,27, 28 renal,29 prostate,19, 30 lung,31 medullablastoma,32 and hepatocellular carcinoma 33. Two reports have been published focusing on EDNRB methylation in nasopharyngeal carcinoma34, 35 but none involving the other head and neck sites.…”

Section: Discussionmentioning

confidence: 99%

KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses

Demokan

Chang

Chuang

et al. 2010

Intl Journal of Cancer

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Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study, we aimed to evaluate to the utility of aberrant promoter hypermethylation for detection in a panel of 10 genes (KIF1A, EDNRB, CDH4, TERT, CD44, NISCH, PAK3, VGF, MAL and FKBP4) in head and neck squamous cell carcinoma (HNSCC) via a candidate gene approach. We investigated methylation of the gene promoters by bisulfite modification and quantitative methylation-specific PCR (Q-MSP) in a preliminary study of a limited cohort of salivary rinses from healthy subjects (n 5 61) and patients with HNSCC (n 5 33). The methylation status of 2 selected genes (EDNRB and KIF1A) were then analyzed in 15 normal mucosa samples from a healthy population, 101 HNSCC tumors and the corresponding salivary rinses from 71 out of the 101 HNSCC patients were collected before treatment. The promoter regions of CDH4, TERT, VGF, MAL, FKBP4, NISCH and PAK3 were methylated in normal salivary rinses while no methylation of CD44 was observed in either normal salivary rinses or tumor samples. However, KIF1A and EDNRB were methylated in 98 and 97% of primary HNSCC tissues respectively and were only methylated in 2 and 6.6% of normal salivary rinses. In addition, KIF1A and EDNRB were methylated in 38 and 67.6% of salivary rinses from HNSCC patients, respectively. Promoter hypermethylation of KIF1A and EDNRB is a frequent event in primary HNSCC, and these genes are preferentially methylated in salivary rinses from HNSCC patients. KIF1A and EDNRB are potential biomarkers for HNSCC detection.Among human malignancies, head and neck cancer is the sixth most common cancer in the world. 1 More than 40,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed in the United States each year, with a mortality rate of 12,000 U.S. deaths annually. Survival rates have not improved significantly for patients with HNSCC in the past 30 years despite active clinical and basic science research addressing this issue. Molecular detection of HNSCC in body fluids has the potential to improve post-treatment surveillance, provide prognostic information, and influence therapy. Body fluids can potentially carry whole cells as well as protein, DNA and RNA species that allow for detection of cellular alterations related to cancer. In previous studies, body fluids such as sputum for lung cancer, 2 urine for urologic tumors, 3 salivary rinses for HNSCC, 4-7 and breast fluid for breast cancer 8 have been used in multiple detection strategies. [9][10][11][12][13] Silencing of tumor suppressor genes by means of promoter hypermethylation plays a role in head and neck carcinogenesis. 5 Measuring promoter hypermethylation by using real time quantitative methylation-specific PCR (Q-MSP) allows an objective, robust, and rapid assessment of promoter methylation status. The ability to quantify methylation

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Section: Discussionmentioning

confidence: 99%

KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses

Demokan

Chang

Chuang

et al. 2010

Intl Journal of Cancer

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“…The EDNRB gene, located on chromosome 13q22, was highly methylated in primary NPC tumor samples, while no methylation was observed in normal nasopharyngeal epithelia (Zhou et al 2007; Lo et al 2002). In patients with NPC, high methylation of the LARS2 gene, which is located at the chromosome 3 common eliminated region-1 ( C3CER1 ) on 3p21.3, has been reported (Zhou et al 2009).…”

Section: Single-gene Studies In Npcmentioning

confidence: 99%

Role of DNA methylation in head and neck cancer

Demokan

Dalay

2011

Clin Epigenet

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Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC.

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“…Polymorphisms in the ENDRB gene were not determined in the present study because hypermethylation of the 5 0 CpG island of EDNRB has been reported in NPC (37,38). The silencing of EDNRB gene expression in NPC is associated with promoter hypermethylation.…”

Section: Discussionmentioning

confidence: 82%

Polymorphisms in the Endothelin-1 and Endothelin A Receptor Genes and Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

Wen

Liu

et al. 2011

Clinical Cancer Research

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Purpose: We aimed to investigate the prognostic role of endothelin-1 (EDN1) and endothelin A receptor (EDNRA) gene polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Experimental Design: Two hundred three consecutive patients with locoregionally advanced NPC were enrolled. Seven potentially functional polymorphisms in the EDN1 and EDNRA genes were determined by ligase detection reaction-PCR method from prospectively collected blood samples. The influence of the genetic polymorphisms on patient overall survival (OS) was analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test.Results:The 5-year OS in patients with EDNRA/H323H TT, TC, and CC genotypes were 81.3%, 62.1%, and 75.0%, respectively (P ¼ 0.004). Patients carrying the heterozygous (TC) or homozygous variant (CC) genotype in EDNRA/H323H were combined for analysis, which revealed that the 5-year OS in patients with TC/CC genotypes was significantly lower than those with the wild-type TT genotype (63.2% vs. 81.3%; P ¼ 0.002). Multivariate analysis showed that EDNRA/H323H polymorphism (HR: 1.95; 95% CI: 1.18-3.23; P ¼ 0.009) and N classification (HR: 1.35; 95% CI: 1.03-1.79; P ¼ 0.03) were independent significant prognostic factors for OS in patients with locoregionally advanced NPC. In contrast, the EDN1 polymorphisms revealed no prognostic value.Conclusions: The EDNRA/H323H polymorphism was a novel and independent prognostic marker for patients with locoregionally advanced NPC. The analysis of EDNRA/H323H polymorphism may help identify patient subgroups at high risk for poor disease outcome.

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Epigenetic and Genetic Alterations of the <i>EDNRB</i> Gene in Nasopharyngeal Carcinoma

Cited by 20 publications

References 56 publications

KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses

KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses

Role of DNA methylation in head and neck cancer

Polymorphisms in the Endothelin-1 and Endothelin A Receptor Genes and Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

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