Inclusion of new microsatellite repeats in allelic loss analysis excludes retention of heterozygosity in the renal cell carcinoma critical region in 3p21

A variety of human cancers, including renal cell carcinoma (RCC), show frequent heterozygous deletion events in 3p21.3. An approximate 400-kb segment from within 3p21.3 is suspect of harboring a tumor suppressor gene, as it is homozygously deleted in three lung cancer cell lines and heterozygously deleted in virtually all lung tumors. Loss of heterozygosity (LOH) studies of this segment are hampered by the absence of highly informative markers. We have identified several new nucleotide repeats that map within this region, and have used these to complement our previous LOH studies in RCC. Our present analysis clearly shows that the common region of homozygous deletions in the lung cancer cell lines is always contained within the smallest region of overlap of heterozygous deletions in RCC. (C) Elsevier Science Inc., 1999. All rights reserved

Inclusion of new microsatellite repeats in allelic loss analysis excludes retention of heterozygosity in the renal cell carcinoma critical region in 3p21

A variety of human cancers, including renal cell carcinoma (RCC), show frequent heterozygous deletion events in 3p21.3. An approximate 400-kb segment from within 3p21.3 is suspect of harboring a tumor suppressor gene, as it is homozygously deleted in three lung cancer cell lines and heterozygously deleted in virtually all lung tumors. Loss of heterozygosity (LOH) studies of this segment are hampered by the absence of highly informative markers. We have identified several new nucleotide repeats that map within this region, and have used these to complement our previous LOH studies in RCC. Our present analysis clearly shows that the common region of homozygous deletions in the lung cancer cell lines is always contained within the smallest region of overlap of heterozygous deletions in RCC. (C) Elsevier Science Inc., 1999. All rights reserved

Genetic analysis of 2 cases of clear cell renal cancer in 2 sisters

Two sisters affected with renal cell carcinoma (RCC) is an extremely rare finding, and may indicate a hereditary pattern or the presence of other predisposing factors. We describe here 2 sisters presenting with clear cell renal cell cancer. Examination for von Hippel-Lindau (VHL)-related features and tuberous sclerosis (M. Bourneville) was negative and both had a normal constitutional karyotype. Cytogenetic analysis of the tumor tissue of both patients showed a translocation involving chromosomes 3 and 5, resulting in loss of 3p sequences and gain of part of 5q. The 5q breakpoints were similar, but the breakpoints at 3p appeared to differ. Allelic imbalance analysis supported our observations. Microsatellite analysis revealed that both sisters inherited different chromosome 3 parental alleles. For chromosome 5, 3 different haplotypes could be deduced, but the chromosome 5 alleles overrepresented in the different tumor tissues were from different parental origin. The development of the 2 RCCs in these 2 sisters thus cannot be explained by the inheritance of a mutated VHL gene located at 3p25, nor by the inheritance of other gene defects at chromosomes 3p or 5q. Although the chance that 2 sisters develop sporadic RCC is very low, in the presented case it is probably coincidental or related to another genetic predisposition. Int. J. Cancer 77:494-497, 1998. (C) 1998 Wiley-Liss, Inc

Analysis of multiple renal cell adenomas and carcinomas suggests allelic loss at 3p21 to be a prerequisite for malignant development

Multiple renal cell rumours from three unrelated patients have been analysed for loss of heterozygosity of 3p, mutation of VHL, and chromosome 7 and 17 imbalances, Loss of 3p alleles is characteristic for clear cell type tumours and the combination of +7, +17 for chromophilic cell type rumours. Thus, we could classify adenomas and carcinomas of the three patients according to the genomic patterns of the tumours. Adenomas appeared to be mostly of the chromophilic cell type. In some adenomas, however, allelic losses of chromosome 3 were detected, pointing to a clear cell phenotype. irrespective of showing loss or retention of the 3p25 region, none of the adenomas had a VHL mutation. Therefore, inactivation of VHL does not seem to be an early event in the development of renal cell rumours. Results of an analysis of regions of loss and retention of alleles of 3p markers in multiple rumours of the individual patients suggest that losses at either 3p25 or 3p12-p14 are associated with adenomas. Additional loss at 3p21 is most likely required to lead to development of a more malignant clear cell carcinoma. (C) 1997 Wiley-Liss, Inc