SCREENING OF THE DIFFERENTIALLY EXPRESSED GENES IN HUMAN RENAL ONCOCYTOMA

Although renal oncocytoma is currently considered to be a rare, benign tumor occurring in the renal cortex, there have been increasing repor ts that tumors initially diagnosed as renal oncocytoma tend to have ma lignant potential and metastatic potential. The mechanisms by which so me tumors initially diagnosed as renal oncocytoma become malignant tum ors remain to be determined. However, it is extremely important to dif ferentially diagnose renal oncocytoma from malignant renal cell carcin oma because the treatment modality of this benign tumor is completely different from that of the malignant tumor. In order to identify any s pecific molecular marker(s) of renal oncocytoma, we have performed ''D ifferential Display of mRNA'' technique using mRNA extracted from norm al kidney tissue and renal oncocytoma obtained from 37 year-old patien t. The clinical and pathological studies of this patient showed the ty pical characteristics of oncocytoma, including abundant mitochondria i n cytoplasm. DNA now cytometry showed normal diploidy in this oncocyto ma. Twenty different polymerase chain reaction (PCR) primer sets were used to compare gene expression patterns of normal and tumor tissues. Under our experimental conditions,. the differential display of mRNA t echnique produced approximately 55 up-regulated and 35 down-regulated bands each representing partial cDNA fragments. Among these differenti ally expressed cDNA fragments, we examined the cDNA sequences of 20 pr ominent polymerase chain reaction bands showing downregulated expressi on patterns in RNA from the oncocytoma tissues. The DNA sequence compa rison analysis using Genbank data base revealed that most clones had u nknown genes. However, one clone showed 98% identity to the yi43f06.s1 clone, which is expressed in the female placenta at birth. Two other clones showed 70% identity to yh8810.ri clone and human IFNAR gene for interferone alpha receptor. Northern blot analysis using these PCR pr oducts as a probe confirmed that the differentially detected PCR bands were not artifacts, but indeed reflected the differential expression of each mRNA during tumorigenesis. We are in the process of further ch aracterizing these genes.