Comprehensive allelotyping of human renal cell carcinomas using microsatellite DNA probes.

Abstract

The von Hippel-Lindau locus on chromosome 3p is a tumor suppressor gene known to be involved in nonpapillary renal cell carcinoma. A previous loss of heterozygosity (LOH) study aimed at determining the allelotype of kidney tumors has indicated that in addition to 3p, chromosome arms 5q, 6q, 10q, llq, 17p, and i9p may also harbor tumor suppressor genes. However, cytogenetic studies reveal that chromosomes 3p, 6q, 8p, 9pq, and 14q most frequently undergo karyotypic changes in renal tumors. To resolve these differences, a collection of microsatellite DNA probes has been used to scan for LOH so that 90%o of individual tumor genomes were rendered informative for allele loss. The assay is capable of detecting quantitative genomic alterations in tumor cells as well. We find that LOH is most frequent for chromosome arm 3p. However, in no tumor is 3p exclusively affected. LOH for 6q, 8p, 9pq, and 14q is also distinctly elevated for both nonpapillary as well as papillary tumors and suggest that many of the tumor suppressor loci involved may be common to the etiology of both forms of kidney cancer.

Frequent breakpoints in the region surrounding FRA3B in sporadic renal cell carcinomas

“…The MIN in oncocytomas observed here is similar to both type I and type II RER + phenotypes that have been reported in other tumors. This is di erent from the observations of Thrash-Bingham et al (1995) who saw only type II RER + phenotype in the oncocytomas they analysed. In addition, they did not observe any LOH in the tumors that had this phenotype.…”

“…There was no association between MIN in these samples and tumor grade or stage. This is similar to the observation of Thrash-Bingham et al (1995).…”

“…However, several investigators have also suggested that 3p deletions were not present in papillary RCC and are con®ned only to nonpapillary RCCs (Zbar et al, 1987;Morita et al, 1991;Kovacs et al, 1989). The benign oncocytomas also do not reveal deletion of 3p sequences (Presti et al, 1993) but exhibit microsatellite instabilities (Thrash-Bingham et al, 1995). The most common microsatellite instability (MIN) associated with oncocytomas is a two to four base pair insertion in a CA repeat (Thrash-Bingham et al, 1995).…”

“…The benign oncocytomas also do not reveal deletion of 3p sequences (Presti et al, 1993) but exhibit microsatellite instabilities (Thrash-Bingham et al, 1995). The most common microsatellite instability (MIN) associated with oncocytomas is a two to four base pair insertion in a CA repeat (Thrash-Bingham et al, 1995). Druck et al (1995) found that 31/35 clear cell RCCs showed a common region of loss between D3S1312 and D3S1481, which¯ank the hRCC (hereditary renal cell carcinoma) translocation breakpoint.…”

Loss of heterozygosity (LOH) at 17q and 14q in human lung cancers

“…Whether or not these observations direct the deletion of the same critical locus will require further study. Cancers of colorectal tract (Chang et al, 1995), kidney (Thrash-Bingham et al, 1995), endometrium (Chang et al, 1995), bladder (Chang et al, 1995), ovary (Cliby et al, 1993b) and neuroblastoma (Takayama et al, 1992) are solid cancers associated with a signi®cant degree of 14q LOH. The proximal end of the region de®ned in our study overlaps with the region de®ned in the ovarian carcinoma study.…”