LOSS OF HETEROZYGOSITY AT THE FAMILIAL RCC T(3-8) LOCUS IN MOST CLEAR-CELL RENAL CARCINOMAS

Previously, we had observed that more than 80% of clear cell renal car cinomas (RCCs) exhibited loss of heterozygosity (LOH) between the micr osatellite markers D3S1285 (in 3p14.1) and D3S1295 (in 3p21.1), a regi on which includes the protein tyrosine phosphatase gamma locus (PTPRG locus, PTP gamma gene) and the 3p14.2 break of the familial RCC-associ ated translocation, t(3;8)(p14.2;q24), which has been hypothesized to affect expression of an RCC suppressor gene or oncogene. Using seven m icro-satellite markers and four markers derived from a PTPRG YAC conti g, we have further delineated the 3p14.2 region of LOH in RCCs. Eighty nine % of clear cell RCCs (31 of 35) showed a common region of loss b etween the D3S1481 and D3S1312 loci which flank the 3p14.2 t(3;8) tran slocation breakpoint and the PTP gamma gene. The PTP gamma gene occupi es similar to 780 kilobase pairs between markers D3S1480 and D3S1312, with its currently defined 5' end greater than 200 kilobase pairs cent romeric to the 3p14.2 translocation break. Although most of the RCCs w ith LOH between D3S1481 and D3S1312 loci have lost at least a portion of one PTP gamma allele, we have tested all known exons of the remaini ng PTP gamma gene in a number of the kidney tumors and have not observ ed mutations. Thus, there may be another gene in the vicinity of the 3 p14.2 break that is important not only in the familial RCCs in the t(3 ;8) family but in the majority of clear cell RCCs.