Study of the OPCML inactivation in epithelial ovarian cancer

Aim of the study: OPCML (opioid binding protein/cell adhesion molecule-like) has a tumor suppressor function in epithelial ovarian cancer (EOC), although the mechanism of its activity is not precisely known. It was suggested that lower OPCML expression may be caused by loss of heterozygosity, epigenetic silencing or the somatic missense mutations. We intended to show dependence between methylation status of ”CpG islands” OPCML and EOC. The location of mutations in OPCML exons was also an aim of this study.
Material and methods: Material was collected from 75 adenocarcinoma serosum ovarii individuals with EOC diagnosed in Centre of Oncology, MSCM Institute. From 20 of them DNA was isolated from peritoneal fluid during decompression reduction of tension. The control group contained 39 cases of cystadenoma ovarii from individuals after mastectomy. We used the Genomic Mini or Sherlock AX kits to DNA extraction. DNA was chemically modificated by sodium bisulfite and was used in MS-PCR reaction. Mutation analysis was made by SSCP analysis and the characteristic samples were sequenced.
Results: In all of EOC diagnosed cases methylation was detected in 46 from 75 cases which represents 61% (p<0,00001) but in control group only 8 of 39 cases (21%) showed methylation in OPCML. Methylation of OPCML ”CpG islands” was detected in 26 out of 55 cases which represents 48% (p=0.0095) of archival material with diagnosed EOC (frozen and paraffined). Methylation was detected in 100% (p<0.00001) of cases in group with DNA isolated from peritoneal fluid. The mutation in OPCML exons was not found.
Conclusions: Epigenetic inactivation of OPCML can lead in ovarian tumorgenesis