DNA methylation in the development of skin cancers

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591092
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Niigata University
• Principal Investigator: FUJIWARA Hiroshi Niigata University, Institute of Medicine and Dentistry, Lecturer, 医歯学系, 講師 (20238637)
• Project Period (FY): 2004 – 2005
• Keywords: squamous cell carcinoma / malignant melanoma / basal cell carcinoma / DNA methylation / E-cadherin / LOH / DNA array

Research Abstract

Genomic DNA was extracted from squamous cell carcinoma of the skin (n=12), malignant melanoma (n=9), and basal cell carcinoma (n=10), and subjected for methylation-specific PCR. DNA methylation in the promoter or 5'- coding region of p16, p14, p15, E-cadherin, von Hippel-Lindau genes were observed in 8 cases, 2 cases, none, 12 cases, and none of the squamous cell carcinoma, respectively, 3 cases, none, none, 4 cases, none of malignant melanoma, and 3 cases, none, none, 4 cases, none of basal cell carcinoma.
In genomic analyses of squamous cell carcinoma loss of heterozygosity or mutation of E-cadherin gene were not detected. Among E-cadherin DNA methylation-positive cases E-cadherin protein expression was abruptly diminished between the tumor and the surrounded normal tissue. The E-cadherin expression in squamous cell carcinoma was suppressed through DNA methylation.
Furthermore, squamous cell carcinoma, malignant melanoma, and basal cell carcinoma, one case each, were subjected to tissue culture, in the medium supplemented with 5'-aza-2'-deoxycytidine or trichostatin A. Extracted RNA was amplified, and hybridized onto Human 1A Oligo Microarray (Agilent). De-methylation of DNA lead the re-expression of tumor suppressor genes.