Identification of novel VHL regulated genes by transcriptomic analysis of RCC10 renal carcinoma cells

摘要

Renal cell carcinomas account for approximately 2% of all adult cancers and cause approximately 100,000 deaths per year worldwide (Parkin et al., 2005). The majority of these tumours (~80%) are classified as 'clear cell' tumours, based on their microscopic appearance (Motzer et al., 1996). Germline mutations of the von Hippel-Lindau {VHL) tumour suppressor gene gives rise to the inherited multi-cancer syndrome VHL disease. Patients are predisposed to a variety of tumours including clear cell renal cell carcinomas (CCRCCs), pheochromocytomas, hemangioblastomas of the retina and central nervous system and benign cysts affecting a variety of organs (Kondo and Kaelin, 2001). Notably, biallelic VHL inactivation also underlies the majority of sporadic CCRCCs, providing an excellent example of Knud-son's two hit model of tumour suppressor gene inactivation (Nickerson et al., 2008). Identification of VHL's role in the renal epithelium has already offered valuable insight into the biology of CCRCC. Typically, CCRCCs present late in the course of the disease, with 30% of patients presenting with metastatic disease (Motzer et al., 1996). Clinically treatment of renal cancer remains challenging. It is hoped that further insight gained from determining VHL's role will lead to new therapeutic approaches.