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

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....

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Bibliographic Details
Published in:	Nature genetics Vol. 34; no. 3; pp. 337 - 343
Main Authors:	Sellar, Grant C, Gabra, Hani, 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
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group 01-07-2003
Subjects:	Adhesion Animals Azacitidine - pharmacology Biological and medical sciences Breast Neoplasms - genetics Carrier Proteins - antagonists & inhibitors Carrier Proteins - genetics Carrier Proteins - metabolism Case-Control Studies Cell Adhesion Molecules - antagonists & inhibitors Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Chromosomes, Human, Pair 11 - genetics Control CpG Islands DNA - genetics DNA - metabolism DNA Methylation Enzyme Inhibitors - pharmacology Female Fundamental and applied biological sciences. Psychology Genes, Tumor Suppressor - physiology Genetic aspects GPI-Linked Proteins Humans Inactivation Loss of Heterozygosity Methylation Mice Mice, Nude Models, Molecular Molecular and cellular biology Mutagenesis, Site-Directed Mutation Mutation - genetics Neoplasms, Glandular and Epithelial - genetics Nerve Tissue Proteins - genetics Ovarian cancer Ovarian Neoplasms - genetics Physiological aspects Reverse Transcriptase Polymerase Chain Reaction Risk factors RNA, Messenger - metabolism Transfection Tumor Cells, Cultured - transplantation Tumor suppressor genes United Kingdom Genetics
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1061-4036 1546-1718
DOI:	10.1038/ng1183