Methylation profiles of sporadic ovarian tumors and nonmalignant ovaries from high-risk women.
OBJECTIVE
The purpose of this research was to examine the DNA methylation profiles of primary sporadic ovarian cancers and ovarian tissues from high-risk women.


METHODS
We analyzed the DNA methylation status of nine cancer-related genes in 49 primary ovarian tumors, 39 nonmalignant ovarian tissues obtained from 16 women with no known risk and from 23 high-risk women with a strong family history of breast and/or ovarian cancer or BRCA1 germ-line mutations, and 11 ovarian cancer cell lines, by methylation-specific PCR.


RESULTS
Our findings are as follows: (a) methylation rates of four of nine genes, RASSF1A (41%), HIC1 (35%), E-cadherin (29%), and APC (18%) were significantly higher in tumors compared with controls. At least one of the four genes was methylated in 76% of the tumors; (b) a low frequency of methylation was present in nonmalignant tissues; (c) no significant differences in methylation frequencies were seen between the nonmalignant ovarian tissues from women at high-risk and those with no known risk of developing ovarian cancer; (d) methylation of the BRCA1 gene was found in 10% of sporadic tumors but in none of the samples from women with a germ-line BRCA1 mutation; and (e) ovarian cancer cell lines showed a similar frequency of methylation to ovarian tumors except for the HIC1 gene.


CONCLUSIONS
Our results suggest that aberrant methylation of specific genes, including two not described previously, may be important in ovarian cancer pathogenesis but not in ovaries at risk for cancer development.
Rathi
Asha
A
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75930, USA.
Virmani
Arvind K
AK
Schorge
John O
JO
Elias
Keren J
KJ
Maruyama
Riichiroh
R
Minna
John D
JD
Mok
Samuel C
SC
Girard
Luc
L
Fishman
David A
DA
Gazdar
Adi F
AF
D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D004587:Electrophoresis, Agar Gel; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012306:Risk; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D004247:DNA; D005982:Glutathione Transferase