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
Cancer Research UK Edinburgh Oncology Unit, University of Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH4 2XR, UK.
Nat Genet. 2003 Jul;34(3):337-43. doi: 10.1038/ng1183.
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.
上皮性卵巢癌（EOC）是妇科恶性肿瘤致死的主要原因，是一种人们了解甚少的疾病。EOC通常表现为晚期，伴有腹腔内局部区域扩散，且内脏转移发生率低，这些都是该疾病的特征。这些特征与疾病生物学相关，而疾病生物学是预后的主要决定因素。EOC是由卵巢表面上皮（OSE；参考文献3）持续发生的基因改变引起的。这些变化的原因尚不清楚，但表现为癌基因激活和肿瘤抑制基因（TSG）失活。我们对11q25杂合性缺失的分析确定了OPCML（也称为OBCAM），它是含免疫球蛋白（Ig）结构域的糖基磷脂酰肌醇（GPI）锚定细胞粘附分子的IgLON家族成员，是EOC中的一个候选TSG。OPCML在EOC中经常通过等位基因缺失和CpG岛甲基化而发生体细胞失活。OPCML在体外和体内都具有与TSG特性一致的功能特征。一名EOC患者的体细胞错义突变显示出明显的功能丧失证据。这些发现表明，OPCML是11q25卵巢癌TSG的极佳候选者。据我们所知，这是首次描述IgLON家族与癌症有关。
