Promoter hypermethylation of the EDNRB gene in nasopharyngeal carcinoma
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AbstractTo identify the epigenetic changes in nasopharyngeal carcinoma (NPC), we performed methylation-sensitive restriction fingerprinting (MSRF) analysis on NPC cell lines and xenografts. A 190 bp sequence methylated in NPC tumors was isolated and showed high homology to the 5' CpG island of the endothelin receptor B (EDNRB) gene. Since the EDNRB gene is commonly inactivated in prostate and bladder cancers, it may be a candidate target gene involved in NPC tumorigenesis. By bisulfite sequencing, we have confirmed that hypermethylation of the 5' CpG island of EDNRB occurred in both xenografts and all 4 cell lines but not in 2 normal nasopharyngeal outgrowths. RT-PCR demonstrated that only original EDNRB transcripts, but not the splicing transcripts, were expressed in normal nasopharyngeal epithelial cells. Loss of the original EDNRB expression was consistently found in 2 xenografts and 3 cell lines with dense methylation patterns. Treatment of these 3 cell lines with 5'-aza-2'-deoxycytidine led to re-expression of the EDNRB transcript and demethylation of its promoter regions. Our results demonstrate that silencing of EDNRB gene expression in NPC is associated with promoter hypermethylation. Using methylation-specific PCR, we also detected methylation of the 5' CpG island of EDNRB in 19/21 (90.5%) primary tumors, while no methylation was found in all 6 normal nasopharyngeal epithelia. The high frequencies of promoter hypermethylation suggest that repression of the EDNRB gene may play a role in the development of NPC. (C) 2002 Wiley-Liss, Inc.
All Author(s) ListLo KW, Tsang YS, Kwong J, To KF, Teo PML, Huang DP
Journal nameInternational Journal of Cancer
Volume Number98
Issue Number5
Pages651 - 655
LanguagesEnglish-United Kingdom
Keywordschromosome 13q; EDNRB; hypermethylation; nasopharyngeal carcinoma; tumor suppressor
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2021-16-01 at 00:03