PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation

Abstract

Array-based comparative genomic hybridization (array-CGH) has good potential for the high-throughput identification of genetic aberrations in cell genomes. In the course of a program to screen a panel of oral squamouscell carcinoma (OSCC), cell lines for genomic copynumber aberrations by array-CGH using our in-house arrays, we identified a 3-Mb homozygous deletion at 10p12 in 1 of 18 cell lines (5.6%). Among seven genes located within this region, expression of PRTFDC1 mRNA was not detected in 50% (9/18) or decreased in 5.6% (1/18) of OSCC cell lines, but detected in normal oral epithelia and restored in gene-silenced OSCC cells without its homozygous loss after treatment with 5-aza-2 0 -deoxycytidine. Among 17 cell lines without a homozygous deletion, the hypermethylation of the PRTFDC1 CpG island, which showed promoter activity, was observed in all nine cell lines with no or reduced PRTFDC1 expression (52.9%). Methylation of this CpG island was also observed in primary OSCC tissues (8/47, 17.0%). In addition, restoration of PRTFDC1 in OSCC cells lacking its expression inhibited cell growth in colony-formation assays, whereas knockdown of PRTFDC1 expression in OSCC cells expressing the gene promoted cell growth. These results suggest that epigenetic silencing of PRTFDC1 by hypermethylation of the CpG island leads to a loss of PRTFDC1 function, which might be involved in squamous cell oral carcinogenesis.

Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene

“…PRTFDC1 belongs to the purine/pyrimidine phosphoribosyltransferase family and is a paralog of HPRT1, but may have lost its ancestral HPRT activity (Keebaugh et al, 2007). However, PRTFDC1 has been reported as a possible tumor-suppressor gene that is frequently silenced by aberrant promoter hypermethylation (Suzuki et al, 2007). To our knowledge PRTFDC1 has not yet been implicated in GWAS of PTSD or other psychiatric disorders and its potential role in the etiology of PTSD remains to be determined.…”

Methylation in oral cancer and pre-cancerous lesions (Review)

“…However, its inhibition in oscc lesions suggests that it may also be affected by epigenetic processes. In a recent study, methylation of this gene was detected in 17% of oscc lesions and was not found to be related to tobacco or alcohol use, gender, age or tumour stage (34).…”

Exploration of Tumor-Suppressive MicroRNAs Silenced by DNA Hypermethylation in Oral Cancer

“…In addition, evidence has emerged that epigenetic mechanisms, such as altered DNA methylation patterns, play a significant role in the silencing of TSGs and contribute to malignant transformation during oral carcinogenesis (16). Recently, genome-wide screenings of DNA copy number alterations for exploring OSCC-associated oncogenes or TSGs have been reported, including by us (17)(18)(19)(20)(21). However, there is no report about abnormal expression of miRNA genes and their genetic or epigenetic alterations in OSCC.…”