Loss of OPCML expression and the co订elation with CpG island methylation and LOH in ovarian serous carcinoma

Purpose: To detect the expression of OPCML in ovarian serous carcinoma and investigate the correlation with CpG island methylation and LOH of OPCML. Methods: 20 normal tissues, 75 ovarian serous tumors, three cell lines, SKOV-3, CAOV3 and 3AO, were detected in OPCML expression by RT-PCR, CpG island methylation by methylation-sensitive restriction enzyme-PCR, and LOH analysis at four microsatellite marks (D11S4085, D11S1320, D11S874 and D11S969). Results: Loss of OPCML expression in ovarian serous carcinomas was significantly higher than in ovarian adenomas and normal tissues. OPCML expression was detectable in 3AO, but not in SKOV-3 and CAOV3. CpG island methylation was found in 53.4% of the carcinomas, while in none of the adenomas or normal tissues. Meanwhile, CpG island methylation was detectable in SKOV-3 and CAOV3, but not in 3AO. The correlation between CpG island methylation and loss of OPCML expression was found in carcinomas. The LOH rate at D11S4085 in carcinomas was significantly higher than that for adenomas and normal tissues. LOH at D11S4085 was also correlated with loss of OPCML expression. Conclusions: These results indicate that loss of OPCML expression occurs frequently in ovarian serous carcinoma. CpG island methylation and LOH are probably two mechanisms of OPCML inactivation.

Ovarian serous carcinoma; OPCML; CpG island methylation; LOH

[1] Thomas G.R., Chen Z., Oechsli M.N., Hendler F.J., Van Waes C.: "Decreased expression of CD80 is a marker for increased tumorigenicity in a new murine model of oral squamous-cell carcinoma". Int. J. Cancer , 1999, 82, 377.

[2] Schofield P.R., McFarland K.C., Hayflick J.S., Wilcox J.N., Cho T.M.,Roy S . et al.: "Molecular characterization of a new immunoglobulin superfamily protein with potential roles in opioid binding and cell contact. EMBO J., 1989, 8,489.

[3] Hachisuka A., Yamazaki T., Sawada J.I., Terao T.: "Characterization and tissue distribution of opioin-binding cell adhesion molecule (OBCAM) using monoclonal antibodies". Neurochem. Int., 1996, 28,373.

[4] Catterall J.B., Jone L.M., Turner G.A.: "Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan". Clin. Exp. Metastasis, 1999, 17, 583.

[5] Sellar G.C., Watt K.P., Rabiasz G.J., Stronach E.A., Li L., Miller E.P. et al.: "OPCML at llq25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer". Nat. Genet., 2003, 34, 337.

[6] Ono K., Tanaka T., Tsunoda T.，比tahara 0., Kihara C., Okamoto A. et al.: "Identification by cDNA microarray of genes involved in ovarian carcinogenesis". Cancer Res., 2000, 60, 5007.

[7] Garnett C.T., Palena C., Chakarborty M., Tsang K.Y., Schlom J., Hodge J.W.: "Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes". Cancer Res., 2004, 64, 7985.

[8] Moretti S., Pinzi C., Berti E., Spallanzani A., Chiarugi A., Boddi V. et al.: "In situ expression of transformation growth factor beta is associated with melanoma progression and correlates with Ki67, HLA-DR and beta 3 integrin expression". Melanoma Res., 1997, 7, 313.

[9] David M.E., Anirban M., Ignacio I.W., Arland A., Jorge A.S., Adi F.G.: "Loss ofheterozygosity at 3p in benign lesions preceding invasive breast cancer". J. Sur. Res., 1999, 83, 13.