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
✍ Scribed by Anke van den Berg; Miriam M. F. Hulsbeek; Debora de Jong; Klaas Kok; Patrick M. J. F. Veldhuis; J. Roche; Charles H. C. M. Buys
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 792 KB
- Volume
- 15
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
In a loss of heterozygosity analysis of 3p, we examined 44 sporadic cases of renal cell carcinoma (RCC) and matched normal tissue with 18 markers distributed over the whole p-arm. The majority of these markers clustered in three regions that have been suggested t o be involved in the development of RCC, namely the p25 region, where the von Hippel Lindau (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) breakpoint occurring in an RCC family. Thirty-one out of these 44 tumors were analyzed with 9 additional markers from the 3p 12-I 4 region t o further delimit the SRO in this region. Our analysis shows that when deletions were detected the 3p2 I region was always included. The 3p2 I markers D3F I5S2 and UBE I1
were always contained within these 3p21 deletions. The t(3;8) breakpoint region showed the lowest percentage of loss of heterozygosity. Moreover, in three cases the t( 3;8) breakpoint region retained heterozygosity, whereas a region more proximal t o the breakpoint 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 at 3p2 I occurred in combination with deletions of either the VHL region, or the region proximal t o the t(3;8), or both, suggestive of multiple gene involvement in the development of sporadic RCC with a primary role of the 3p21 region.