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 3p14.1) and D3S1295 (in 3p21.1), a region which includes the protein tyrosine phosphatase γ locus (PTRG locus, PTPγ gene) and the 3p14.2 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 microsatellite markers and four markers derived from a PTPRG YAC contig, 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 between the D3S1481 and D3S1312 loci which flank the 3p14.2 t(3;8) translocation breakpoint and the PTPγ gene. The PTPγ gene occupies ∼780 kilobase pairs between markers D3S1480 and D3S1312, with its currently defined 5′ end greater than 200 kilobase pairs centromeric to the 3p14.2 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 3p14.2 break that is important not only in the familial RCCs in the t(3;8) family but in the majority of clear cell RCCs.

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This work was supported by USPHS Grant CA51083, by a gift from Mr. R. R. M. Carpenter III and Mrs. Mary K. Carpenter, by U.S.-Poland MCSJFII Grant MZ/HHS-91-75, the Polish National Scientific Committee Grant 408899101, and a European Communities Programme Grant BMH1-CT-0156.

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