The Extent of Chromosomal Losses and the Status of CpG Methylation in Squamous Cell Carcinoma of the Head and Neck

Cho, Kwang Jae; Kim, Min Sik; Rhyu, Mun Gan; Cho, Seung Ho

Abstract

BACKGROUND AND OBJECTIVES
Carcinogenesis is known to arise as a result of the accumulation of genetic alterations including unilateral chromosomal losses and epigenetic modification. In this study, we investigated the extent of chromosomal losses and the status of CpG methylation in squamous cell carcinoma of the head and neck in relation to the clinicopathologic factors. SUBJECTS AND METHOD: A total of 20 tumor foci from 12 cases were examined wtih PCR-based loss of heterozygosity (LOH) analysis using a panel of 41 microsatellite markers on 8 chromosomes and a total of 10 tumor foci from 5 cases were examined with methylation-specific PCR on 2 extragenic regions of the 3 cancer-linked genes. RESULTS: In 20 tumor foci, LOH was found most frequently on the chromosome 8p. Multiple tumor foci of a given case had the same or a similar extent of chromosomal losses and yielded an overall mean value of 5.5 per tumor focus. Even though the tumor foci showed histological homogeneity, they revealed genetical heterogeneity. The relation between methylation changes between the paired normal mucosa and tumor site was variable and 10 tumor sites examined for the methylation status of 6 extragenic regions showed 21 (35%) hypomethylation changes, 6 (10%) hypermethylation changes, and 33 (55%) no methylation changes. The degree of methylation changes indicated the tendency to cluster in the range of U1 and M1 low-grade changes. With respect to relationship between bet methylation changes and clinicopathologic factors, hypomethylation changes were dominant in those cases with increased depth of invasion. CONCLUSION: These results showed that multiple intratumoral foci of the head and neck cancer patients were generally under the influence of a similar level of chromosomal losses and hypomethylation changes.