MAJOR ROLE FOR A 3P21 REGION AND LACK OF INVOLVEMENT OF THE T(3-8) BREAKPOINT REGION IN THE DEVELOPMENT OF RENAL-CELL CARCINOMA SUGGESTED BY LOSS OF HETEROZYGOSITY ANALYSIS

In a loss of heterozygosity analysis of 3p, we examined 44 sporadic ca ses of renal cell carcinoma (RCC) and matched normal tissue with 18 ma rkers distributed over the whole p-arm. The majority of these markers clustered in three regions that have been suggested to be involved in the development of RCC, namely the p25 region, where the von Hippel Li ndau (VHL) gene is located; the p21 region, which has been identified as a common region of overlap (SRO) of heterozygous deletions; and the p14 region, which is the location of the constitutional t(3;8) breakp oint occurring in an RCC family. Thirty-one our of these 44 tumors wer e analyzed with 9 additional markers from the 3p12-14 region to furthe r delimit the SRO in this region. Our analysis shows that when deletio ns were detected the 3p21 region was always included. The 3p21markers D3F15S2 and UBEIL were always contained within these 3p21 deletions. T he t(3;8) breakpoint region showed the lowest percentage of loss of he terozygosity. Moreover, in three cases the t(3;8) breakpoint region re tained heterozygosity, whereas a region more proximal to the breakpoin t showed allelic losses. This supports exclusion of the t(3;8) region from a role in the development of sporadic RCC. In a number of tumors, two or three 3p regions with allelic losses were present separated by a region of retention of heterozygosity. In these tumors, deletions a t 3p21 occurred in combination with deletions of either the VHL region , or the region proximal to the t(3;8), or both, suggestive of multipl e gene involvement in the development of sporadic RCC with a primary r ole of the 3p21 region. (C) 1996 Wiley-Liss, Inc.