title: FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer.
abstract: Epithelial ovarian cancer is one of the most lethal of gynecological malignancies. Due to its lack of early symptoms, detection usually occurs when the tumor is no longer confined to the ovary. We previously identified Fbxw15, a gene encoding an F-box protein in the mouse ovary, and showed that its expression is developmentally regulated. Here we report the molecular analysis of its human homologue, FBXW12 in epithelial ovarian tumors. To search for FBXW12 gene mutations, we PCR-amplified and sequenced the coding region of FBXW12, the gene's 5-untranslated region and the proximal promoter in each of 30 EOC tumors. Promoter methylation was determined by DNA bisulfite conversion, followed by methylation specific PCR. FBXW12 intracellular localization was identified by means of immunohistochemistry. A complete deletion of the gene's coding region, the 5'-UTR and the proximal promoter, was observed in 3 EOC samples. Eight of the remaining 27, had a deletion of the 5'-UTR, and the proximal promoter. FBXW12 mRNA was detected in 2 of the 19 samples without deletions. The methylation specific PCR results demonstrated CpGs methylation in the FBXW12 proximal promoter. Immunohistochemistry assay revealed that within the normal ovary, FBXW12 has an oocyte specific expression, whereas in EOC samples it is present in the ovarian surface epithelium. Our results indicate that the FBXW12 gene is deleted in approximately ten percent of the EOC cases studied; such deletions comprised either the FBXW12 promoter or the mRNA-encoding region. Moreover, FBXW12 could be epigenetically silenced by CpGs methylation in some of these EOC cases.
authors.affiliation: Research Unit in Metabolic Diseases, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social México 06720, D.F., México.
authors.forename: Elsa
authors.initials: E
authors.lastname: De La Chesnaye
authors.affiliation: Research Unit in Obesity, Facultad de Medicina, Universidad Nacional Autónoma de México; Obesity Clinic, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" México 14000, D.F., México.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Méndez
authors.affiliation: Research Unit in Oncologic Diseases, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social México 06720, D.F., México.
authors.forename: Ricardo
authors.initials: R
authors.lastname: López-Romero
authors.affiliation: Research Unit in Metabolic Diseases, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social México 06720, D.F., México.
authors.forename: María
authors.initials: M
authors.lastname: De Los Angeles Romero-Tlalolini
authors.affiliation: Department of Research, Hospital de la Mujer México 11340, D.F., México.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Vergara
authors.affiliation: Research Unit in Oncologic Diseases, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social México 06720, D.F., México.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Salcedo
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center Beaverton, OR 97006, USA.
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Ojeda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D019175:DNA Methylation; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D044783:F-Box Proteins; C487998:FBXW12 protein, human
keywords: F-box proteins; epithelial ovarian cancer