Frequently deleted loci on chromosome 9 may harbor several tumor suppressor genes in human renal cell carcinoma

Purpose: Loss of various loci on chromosome 9 has been reported in various cancers. To determine the frequency of deletions at different loci of chrom osome 9 in renal cell carcinoma microdissected samples of normal renal epit helium and carcinoma from the same patients were analyzed. Materials and Methods: DNA was isolated from microdissected sections of nor mal and tumor cells of 60 renal specimens, amplified by polymerase chain re action and analyzed for loss of heterozygosity on chromosome 9 using the 16 microsatellite markers D9S178, D9S157, D9S274, D9S168, D9S285, D9S156, D9S 1839, D9S162, IFNA, D9S736, D9S171, D9S1749, D9S273D9S270, D9S153 and D9S17 0. Loss of heterozygosity was analyzed by a polymerase chain reaction based technique developed at our laboratory. Results: This study showed a high incidence of loss of heterozygosity on ch romosome 9 in renal cell carcinoma. Of 60 cases 44 (73%), 24 (40%) and 14 ( 23%) showed loss of heterozygosity at a minimum of 1, at a minimum of 3 and at 4 or more loci, respectively. The main deletion was found on the 9p21 r egion at loci DS171 in 38% of cases, D9S1749 in 42% and DS270 in 14%. Overa ll deletion on chromosome 9p21 was noted in 57% of renal cancer cases. Othe r deleted regions were on chromosome 9p'0022 to 23 at loci D9S157 in 37% of cases, D9S274 in 20%, D9S168 in 27%, D9S285 in 20%, D9S156 in 12%, D9S1839 in 17% and D9S162 in 24%. Overall deletion at chromosome 9q32 to 33 was no ted in 46% of renal cell carcinoma cases. Chromosome 9q32 to 33 also showed deletion at locus D9S170 in 22% of renal cell carcinoma cases. When we com pared the incidence of deletion at various loci on chromosome 9 according t o renal cell carcinoma grade, we found a higher rate of deletion in advance d grades of renal cell carcinoma. A candidate target tumor suppressor gene, p16 (MTS-1/CDKN2), has been identified within the 9p21 deleted region in v arious cancers. In our study the expression of p16 protein was absent or lo w in renal cell cancer samples, suggesting that loss of the p 16 gene may b e involved in renal cell carcinogenesis. Conclusions: Our study demonstrates a high incidence of loss of heterozygos ity on chromosome 9, mainly 9p21 and 9p22 to 23, in renal cell carcinoma, s uggesting several putative tumor suppressor genes on these regions. The ide ntification of other tumor suppressor genes on the 9p21 and 9p22 to 23 regi ons warrants further studies.