OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer.

Sellar, Grant C; Watt, Karen P; Rabiasz, Genevieve J; Stronach, Euan A; Li, Li; Miller, Eric P; Massie, Charles E; Miller, Jayne; Contreras-Moreira, Bruno; Scott, Diane; Brown, Iain; Williams, Alastair R; Bates, Paul A; Smyth, John F; Gabra, Hani

Sellar, Grant C; Watt, Karen P; Rabiasz, Genevieve J; Stronach, Euan A; Li, Li; Miller, Eric P; Massie, Charles E; Miller, Jayne; Contreras-Moreira, Bruno; Scott, Diane; Brown, Iain; Williams, Alastair R; Bates, Paul A; Smyth, John F; Gabra, Hani.

Afiliación

Sellar GC; Cancer Research UK Edinburgh Oncology Unit, University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK. grant.sellar@cancer.org.uk

Nat Genet ; 34(3): 337-43, 2003 Jul.

Article en En | MEDLINE | ID: mdl-12819783

RESUMEN

Epithelial ovarian cancer (EOC), the leading cause of death from gynecological malignancy, is a poorly understood disease. The typically advanced presentation of EOC with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases are hallmarks of the disease. These features relate to the biology of the disease, which is a principal determinant of outcome. EOC arises as a result of genetic alterations sustained by the ovarian surface epithelium (OSE; ref. 3). The causes of these changes are unknown but are manifest by activation of oncogenes and inactivation of tumor-suppressor genes (TSGs). Our analysis of loss of heterozygosity at 11q25 identified OPCML (also called OBCAM), a member of the IgLON family of immunoglobulin (Ig) domain-containing glycosylphosphatidylinositol (GPI)-anchored cell adhesion molecules, as a candidate TSG in EOC. OPCML is frequently somatically inactivated in EOC by allele loss and by CpG island methylation. OPCML has functional characteristics consistent with TSG properties both in vitro and in vivo. A somatic missense mutation from an individual with EOC shows clear evidence of loss of function. These findings suggest that OPCML is an excellent candidate for the 11q25 ovarian cancer TSG. This is the first description to our knowledge of the involvement of the IgLON family in cancer.

Asunto(s)

Proteínas Portadoras/genética; Moléculas de Adhesión Celular/genética; Cromosomas Humanos Par 11/genética; Genes Supresores de Tumor/fisiología; Pérdida de Heterocigocidad; Neoplasias Glandulares y Epiteliales/genética; Neoplasias Ováricas/genética; Animales; Azacitidina/farmacología; Neoplasias de la Mama/genética; Proteínas Portadoras/antagonistas & inhibidores; Proteínas Portadoras/metabolismo; Estudios de Casos y Controles; Moléculas de Adhesión Celular/antagonistas & inhibidores; Moléculas de Adhesión Celular/metabolismo; Islas de CpG; ADN/genética; ADN/metabolismo; Metilación de ADN; Inhibidores Enzimáticos/farmacología; Femenino; Proteínas Ligadas a GPI; Humanos; Ratones; Ratones Desnudos; Modelos Moleculares; Mutagénesis Sitio-Dirigida; Mutación/genética; Proteínas del Tejido Nervioso/genética; ARN Mensajero/metabolismo; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Transfección; Células Tumorales Cultivadas/trasplante

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cromosomas Humanos Par 11 / Proteínas Portadoras / Moléculas de Adhesión Celular / Genes Supresores de Tumor / Neoplasias Glandulares y Epiteliales / Pérdida de Heterocigocidad Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2003 Tipo del documento: Article Pais de publicación: Estados Unidos

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