Opioid-binding protein/cell adhesion molecule-like (OPCML) gene and promoter methylation status in women with ovarian cancer.
OBJECTIVE
The expression profile of the OPMCL gene was studied to find out if there was any evidence of a CpG island methylator phenotype and if there was an association of CpG island methylation with the gene downregulation in women with ovarian cancer.


METHODS
Expression of OPCML in 43 ovarian cancer tumor samples and in 4 normal ovaries was determined by RT-PCR. Methylation status of OPCML promoter region was studied with methylation-specific PCR (MSP) method. Possible associations with selected clinicopathologic variables: FIGO stage, histological grade, patient's age and menopausal status were tested.


RESULTS
In all normal ovarian samples OPCML mRNA was present, but it was not detectable in 24 of 43 ovarian cancer cases. We have not found the relationship between age and menopausal status with the presence of RTPCR product of OPCML. Hypermethylation of OPCML was not correlated to FIGO stage, however, in 80% of cases with methylated OPCML early clinical stage was also present. Tumor grading and histological type had no significant influence on the presence of hypermethylation of OPCML gene. In 20 of 43 cases of ovarian cancer methylated product of MSP amplification was present. In a group of OPCMLmRNA-negative tumors there were 75% of cases with hypermethylated exon of OPCML and the correlation between these variables was statistically significant (chi2 =17.7; p=0,00003). No promoter hypermethylation of the studied gene was found in normal ovaries.


CONCLUSIONS
Reduced OPCMPL gene expression in ovarian cancer in comparison to normal ovaries could be related to the hypermethylation of promoter region. This epigenetic alteration may be the reason of gene silencing and the loss of suppressor function.
Czekierdowski
Artur
A
1st Department of Gynecology of the Medical University in Lublin, Poland. ginonkol@am.lublin.pl
Czekierdowska
Sylwia
S
Szymanski
Marek
M
Wielgos
Miroslaw
M
Kaminski
Pawel
P
Kotarski
Jan
J
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C059785:OPCML protein, human; D012333:RNA, Messenger