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 carcinomas (RCCs) exhibited loss of heterozygosity (LOH) between the microsatellite markers D3S1285 (in 3pl4.1) and D3S1295 (in 3p21.1), a region which includes the protein tyrosine phosphatase γ locus (PTPRG locus, PTPγ gene) and the 3pl4.2 break of the familial RCC-associated translocation, t(3;8)(p14.2;q24), which has been hypothesized to affect expression of an RCC suppressor gene or oncogene. Using seven micro-satellite markers and four markers derived from a PTPRG YAC contig, we have further delineated the 3pl4.2 region of LOH in RCCs. Eighty-nine % of clear cell RCCs (31 of 35) showed a common region of loss between the D3S14S1 and D3S1312 loci which flank the 3pl4.2 t(3;8) translocation breakpoint and the PTPy gene. The PTPy gene occupies −780 kilobase pairs between markers D3S1480 and D3S1312, with its currently defined 5′ end greater than 200 kilobase pairs centromeric to the 3pl4.2 translocation break. Although most of the RCCs with LOH between D3S1481 and D3S1312 loci have lost at least a portion of one PTPγ allele, we have tested all known exons of the remaining PTPγ gene in a number of the kidney tumors and have not observed mutations. Thus, there may be another gene in the vicinity of the 3pl4.2 break that is important not only in the familial RCCs in the t(3;8) family but in the majority of clear cell RCCs.