FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer

Elsa De La Chesnaye, Juan Pablo Méndez, Ricardo López-Romero, María de los Angeles Romero-Tlalolini, María Dolores Vergara, Mauricio Salcedo, Sergio Ojeda

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)10192-10203
    Number of pages12
    JournalInternational Journal of Clinical and Experimental Pathology
    Volume8
    Issue number9
    StatePublished - 2015

    Fingerprint

    F-Box Proteins
    Methylation
    5' Untranslated Regions
    Ovary
    Genes
    Polymerase Chain Reaction
    Neoplasms
    Immunohistochemistry
    Messenger RNA
    Gene Deletion
    Oocytes
    Epithelium
    Ovarian epithelial cancer
    Mutation
    DNA

    Keywords

    • Epithelial ovarian cancer
    • F-box proteins

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Histology

    Cite this

    De La Chesnaye, E., Méndez, J. P., López-Romero, R., Romero-Tlalolini, M. D. L. A., Vergara, M. D., Salcedo, M., & Ojeda, S. (2015). FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer. International Journal of Clinical and Experimental Pathology, 8(9), 10192-10203.

    FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer. / De La Chesnaye, Elsa; Méndez, Juan Pablo; López-Romero, Ricardo; Romero-Tlalolini, María de los Angeles; Vergara, María Dolores; Salcedo, Mauricio; Ojeda, Sergio.

    In: International Journal of Clinical and Experimental Pathology, Vol. 8, No. 9, 2015, p. 10192-10203.

    Research output: Contribution to journalArticle

    De La Chesnaye, E, Méndez, JP, López-Romero, R, Romero-Tlalolini, MDLA, Vergara, MD, Salcedo, M & Ojeda, S 2015, 'FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer', International Journal of Clinical and Experimental Pathology, vol. 8, no. 9, pp. 10192-10203.
    De La Chesnaye E, Méndez JP, López-Romero R, Romero-Tlalolini MDLA, Vergara MD, Salcedo M et al. FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer. International Journal of Clinical and Experimental Pathology. 2015;8(9):10192-10203.
    De La Chesnaye, Elsa ; Méndez, Juan Pablo ; López-Romero, Ricardo ; Romero-Tlalolini, María de los Angeles ; Vergara, María Dolores ; Salcedo, Mauricio ; Ojeda, Sergio. / FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer. In: International Journal of Clinical and Experimental Pathology. 2015 ; Vol. 8, No. 9. pp. 10192-10203.
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    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.",
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