full access: DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines

Table 1

Histology and clinical characteristics of primary ovarian tumors. (serous, endometrioid, clear cell - CA125 levels, menopausal status,patient age)

Background

Epithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood.

Significance: The significant difference in DNA methylation profiles between ovarian cancer cell lines and tumors underscores the need to be cautious in using cell lines as tumor models for molecular studies of ovarian cancer and other cancers. Similarly, the distinct methylation profiles of the different histological types of ovarian tumors reinforces the need to treat the different histologies of ovarian cancer as different diseases, both clinically and in biomarker studies.

Discussion: We quantitatively assessed the DNA methylation status of 1,505 CpG sites, (associated with 808 genes), in 15 commonly used ovarian cancer cell lines and 27 primary ovarian tumors, 15 serous (55.5%), 9 endometrioid (33.3%) and 3 clear cell (11.1%). These proportions roughly reflect the relative frequencies of the different histologies of ovarian carcinoma diagnosed in the US (serous tumors 50%, endometrioid 25–30%, mucinous 10–15%, clear cell 5%, and others <5%. .... Although the numbers of some subtypes, such as clear cell tumors, were small, unsupervised and supervised analyses of the DNA methylation profiles of the primary tumors indicate clear differences between the histological types....The distinctness of the DNA methylation profiles of the histological subtypes is suggestive of different tumorigenic mechanisms and/or cells of origin and underscores the need to view the different histological types of ovarian cancer as different diseases. While this notion is common knowledge among clinicians, and is reflected in studies of tumor gene expression and protein expression, regrettably, it is often ignored in molecular diagnostic studies, and all cases of ovarian cancer are still treated similarly in clinic despite their acknowledged differences in pathology....Additional profiling of primary tumors and corresponding normal tissues (fallopian tube, ovarian surface epithelium, peritoneum or endometrium) as well as measurements of methylated DNA in candidate detection media (blood or proximal fluids) in both health and disease will help define the natural history of ovarian cancers and critically assess the potential utility of DNA methylation based biomarkers in combating ovarian cancer.