Identification and investigation of candidate tumour suppressor genes from chromosome 11q24-q25 in epithelial ovarian cancer

Abstract

Approximately 7000 women are diagnosed with epithelial ovarian cancer every year in the UK. The majority of these women will die from their disease. Understanding the molecular biology of epithelial ovarian cancer will lead ultimately to the identification of targets for therapeutic intervention and diagnosis.Tumour suppressor genes play a crucial role in carcinogenesis yet few of these genes have been identified in sporadic ovarian cancer. Previously published studies suggest that a tumour suppressor gene in epithelial ovarian cancer is located at chromosome 1 lq24-5. To identity the tumour suppressor gene from this region 1 have performed the largest LOH study in this region to date using 16 polymorphic microsatellite markers and DNA pairs from 1 12 patients with epithelial ovarian cancer. The results from this study have led to the identification of several critical regions of LOH. One ofthese regions unambiguously identifies OBCAM as a strong candidate tumour suppressor gene.OBCAM is an extracellular GPI-linked cell adhesion molecule that is shown in this work to be almost ubiquitously inactivated in epithelial ovarian cancer by a combination of LOH and methylation. Furthermore 1 have demonstrated that it is a functional tumour suppressor both invitro and invivo.OBCAM is the first member of the IgLON family of proteins identified as likely to be important in cancer.