Methylation of CpG island promoters in uveal melanoma.
BACKGROUND
Inactivation of tumour-related genes by promoter hypermethylation is a common epigenetic event in the development of a variety of tumours.


OBJECTIVE
To investigate in primary uveal melanoma the status of promoter methylation of genes thought to be involved in tumour development: p16, TIMP3, RASSF1, RARB, FHIT, hTERT and APC.


METHODS
Gene promoter methylation was studied by methylation-sensitive single-strand conformation analysis and dot-blot assay in a series of 23 primary uveal melanomas. All DNA samples were obtained from paraffin-embedded formalin-fixed tissue blocks.


RESULTS
hTERT promoter methylation was found with a relatively high frequency (52%). Promoter methylation of p16, TIMP3, RASSF1, RARB, FHIT and APC was a rare event. For none of these genes did promoter methylation exceed 15% of tumour samples, and, for some genes (FHIT and APC), no methylation was found at all. Furthermore, promoter methylation was absent in 39% (9/23) of cases. In only 22% (5/23) of cases was hypermethylation of at least two promoters observed.


CONCLUSIONS
Promoter methylation of hTERT is a regular event in uveal melanoma. Hypermethylation of the other genes studied does not seem to be an essential element in the development of this tumour. As promoter methylation of APC, RASSF1 and RARB is often observed in cutaneous melanoma, these results suggest that different epigenetic events occur in the development of cutaneous and uveal melanoma.
Moulin
A P
AP
Institute of Pathology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 25, 1011 Lausanne, Switzerland.
Clément
G
G
Bosman
F T
FT
Zografos
L
L
Benhattar
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014604:Uveal Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm