Frequent promoter hypermethylation of RASSF1A and p16INK4a and infrequent allelic loss other than 9p21 in betel-associated oral carcinoma in a Vietnamese non-smoking/non-drinking female population.

Abstract

BACKGROUND:

Betel-chewing, a risk factor for oral carcinoma, is a common habit of elderly Vietnamese females, but concomitant habits of tobacco and alcohol are uncommon.

METHODS:

In the present study, 36 paraffin-embedded betel-associated oral carcinoma samples including 27 squamous cell carcinoma (SCC) and nine verrucous carcinomas (VC) were analyzed for the hypermethylation of tumor suppressor genes (TSGs) and loss of heterozygosity (LOH) of important TSG loci. Methylation-specific polymerase chain reaction (MSP) was used to identify promoter hypermethylation of p16INK4a and RASSF1A. For LOH analysis, 39 microsatellite markers at 12 chromosomal arms were examined by p olymerase chain reaction (PCR)-based microsatellite assay.

RESULTS:

Hypermethylation of p16IKN4a was detected in 63% of SCC and 67% of VC. In addition, LOH at 9p21 (locus for p16INK4a) was 58% for SCC and 22% for VC, and hypermethylation of RASSF1A was 93% for SCC and 100% for VC. LOH at 3p21.3-3p22.1 (where RASSF1A is located) was detected in only 12% of SCC and 0% of VC. LOH of other chromosomal arms were infrequent.

CONCLUSION:

As LOH for chromosomes other than 9p was uncommon, epigenetic silencing of RASSF1A and p16INK4a gene expression by promoter hypermethylation may play a critical role in betel-associated oral carcinogenesis.

• Authors: Tu Ngoc Tran, Yenchun Liu, Minoru Takagi, Akira Yamaguchi, Hiroaki Fujii
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 34 Issue 3 Pg. 150-6 (Mar 2005) ISSN: 0904-2512 [Print] Denmark
• PMID: 15689228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16
• DNA, Neoplasm
• RASSF1 protein, human
• Tumor Suppressor Proteins

Topics

• Aged
• Aged, 80 and over
• Areca (adverse effects)
• Carcinoma (genetics)
• Carcinoma, Squamous Cell (genetics)
• Carcinoma, Verrucous (genetics)
• Chromosomes, Human, Pair 9 (genetics)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• DNA Methylation
• DNA, Neoplasm (genetics)
• Female
• Gene Silencing
• Humans
• Loss of Heterozygosity
• Microsatellite Repeats (genetics)
• Mouth Neoplasms (genetics)
• Promoter Regions, Genetic (genetics)
• Thailand
• Tumor Suppressor Proteins (genetics)