title: Genetic and epigenetic alterations of steroidogenic factor‑1 in ovarian             tumors.
abstract: Steroidogenic factor-1 (SF‑1), the product of the NR5A1 gene, is an essential             transcription factor that is known to regulate steroidogenesis in ovarian epithelia,             including the synthesis of progesterone, a suppressor of ovarian cancer. Expression             of the SF‑1 protein, a potential ovarian tumor suppressor, has been demonstrated             in normal OSE cells, but is lost in most ovarian tumors and ovarian tumor cell             lines. We examined loss of heterozygosity (LOH) and promoter methylation as potential             mechanisms that may explain the loss of SF‑1 protein in ovarian tumor tissues.             Genotyping of three NR5A1 SNPs in matched tumor/normal tissues identified LOH             in 16/36 (44%) of the ovarian tumors successfully analyzed, and somatic mutations             (gain of allele) in 10% of the tumors. Furthermore, a methylation-sensitive restriction             enzyme method was used to demonstrate statistically significant (p<0.0001)             increase in the frequency of NR5A1 gene methylation in ovarian tumors (36/46;             78%) versus normal ovaries (1/11; 9%). These data suggest that the SF‑1 encoding             gene exhibits frequent genetic (LOH/base substitution) and epigenetic (methylation)             somatic alterations in ovarian tumors. These data also present novel molecular             mechanisms that may explain the loss of SF‑1 protein in ovarian tumors, and its             potential role in ovarian carcinogenesis.
authors.affiliation: Ohio Department of Health, Columbus, OH 43215, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Miller
authors.forename: Nobel
authors.initials: N
authors.lastname: Bhasin
authors.forename: Heather
authors.initials: H
authors.lastname: Urrego
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Moroz
authors.forename: Brian G
authors.initials: BG
authors.lastname: Rowan
authors.forename: Meera S
authors.initials: MS
authors.lastname: Ramayya
authors.forename: Nick M
authors.initials: NM
authors.lastname: Makridakis
mesh_terms: D000328:Adult; D063646:Carcinogenesis; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D054339:Steroidogenic Factor 1 / Q000235:genetics*
chemical_list: C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1