Identification of a novel methylated gene in nasopharyngeal carcinoma: TTC40.

Abstract

To further explore the epigenetic changes in nasopharyngeal carcinoma (NPC), methylation-sensitive arbitrarily primed PCR was performed on NPC biopsies and nontumor nasopharyngeal samples. We have shown mainly two DNA fragments that appeared to be differentially methylated in NPCs versus nontumors. The first, defined as hypermethylated, corresponds to a CpG island at the 5'-end of the tetratricopeptide repeat domain 40 (TTC40) gene, whereas the second, defined as hypo-methylated, is located on repetitive sequences at chromosomes 16p11.1 and 13.1. Thereafter, the epigenetic alteration on the 5'-TTC40 gene was confirmed by methylation-specific PCR, showing a significant aberrant methylation in NPCs, compared to nontumors. In addition, the bisulfite sequencing analysis has shown a very high density of methylated cytosines in C15, C17, and X666 NPC xenografts. To assess whether TTC40 gene is silenced by aberrant methylation, we examined the gene expression by reverse transcription-PCR. Our analysis showed that the mRNA expression was significantly lower in tumors than in nontumors, which is associated with 5'-TTC40 gene hypermethylation. In conclusion, we found that the 5'-TTC40 gene is frequently methylated and is associated with the loss of mRNA expression in NPCs. Hypermethylation of 5'-TTC40 gene might play a role in NPC development; nevertheless, other studies are needed.

• Authors: Wajdi Ayadi, Nesrine Allaya, Hanèn Frikha, Emna Trigui, Abdelmajid Khabir, Abdelmonem Ghorbel, Jamel Daoud, Mounir Frikha, Ali Gargouri, Raja Mokdad-Gargouri
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 691742 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 25101295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CFAP46 protein, human
• Cytoskeletal Proteins
• Neoplasm Proteins
• Proteins
• Azacitidine

Topics

• Animals
• Azacitidine (pharmacology)
• Carcinoma
• Cell Line, Tumor
• CpG Islands
• Cytoskeletal Proteins
• DNA Methylation (genetics)
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• High-Throughput Nucleotide Sequencing
• Humans
• Mice
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (genetics, pathology)
• Neoplasm Proteins (biosynthesis, genetics)
• Promoter Regions, Genetic
• Proteins (genetics)
• Xenograft Model Antitumor Assays