Methylation of death-associated protein kinase in ovarian carcinomas

Abstract

Death-associated protein (DAP) kinase is a serine/threonine kinase that plays an integral role in apoptosis and metastasis. The purpose of our study was to determine the methylation status of DAP kinase in ovarian carcinomas. Thirty-one patients with histologically confirmed epithelial ovarian cancers treated at Roswell Park Cancer Institute, Buffalo, New York, between 1987 and 1999 were studied. Sixty-two samples were examined for DAP kinase methylation status: 1 normal human genomic DNA sample from a healthy individual, 1 transformed normal surface ovarian epithelial cell line (IOSE, from Dr Nancy Auersperg, Vancouver, Canada), 2 ovarian carcinoma cell lines (OVCAR3 and A2780), 1 ovarian serous cystadenoma, and 30 ovarian carcinomas. Additionally, peripheral blood DNA was examined from the patients with the serous cystadenoma and ovarian carcinomas. Methylation-specific polymerase chain reaction was performed using primers designed for the unmethylated and methylated promoter regions. The DAP kinase gene was unmethylated in both the normal human genomic DNA sample and the transformed normal surface epithelial ovarian cell line. The two ovarian cancer cell lines were methylated. In the 30 patients with malignant disease, methylation of DAP kinase was observed in 20 (67%). Peripheral blood DNA was available in 26 (87%) of the 30 patients. Comparison of the paired samples indicated that 14 (54%) were methylated and 12 (46%) were unmethylated. There was no correlation between the DAP kinase methylation status and stage, grade, histology, or survival. Methylation of CpG islands in the promoter region of the DAP kinase gene is common in peripheral blood DNA and tissue samples of patients with ovarian carcinomas. This molecular aberration may represent a potential target for therapeutic intervention.