Comprehensive allelotyping of human renal cell carcinomas using microsatellite DNA probes

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• The von Hippel-Lindau (VHL) locus on chromosome 3p is a known tumor suppressor gene implicated in nonpapillary renal cell carcinoma.
• Previous studies suggest multiple chromosome arms harbor tumor suppressor genes involved in kidney cancer, but findings differ between loss of heterozygosity (LOH) and cytogenetic analyses.

Purpose of the Study:

• To resolve discrepancies between LOH and cytogenetic studies regarding tumor suppressor genes in kidney tumors.
• To identify frequently altered chromosomal regions in both papillary and nonpapillary renal cell carcinoma.

Main Methods:

• Utilized a panel of microsatellite DNA probes to scan for LOH across 90% of individual tumor genomes.
• Employed an assay capable of detecting quantitative genomic alterations in tumor cells.

Main Results:

• Loss of heterozygosity (LOH) was most frequent on chromosome arm 3p, but it was not exclusively affected in any tumor.
• Significantly elevated LOH was observed for chromosome arms 6q, 8p, 9pq, and 14q in both nonpapillary and papillary renal tumors.
• These chromosomal alterations were detected quantitatively within tumor cells.

Conclusions:

• Multiple chromosomal arms, including 3p, 6q, 8p, 9pq, and 14q, frequently undergo alterations in renal tumors.
• The identified tumor suppressor loci may be common to the development of both nonpapillary and papillary renal cell carcinoma.
• This comprehensive LOH analysis provides a refined allelotype for kidney tumors.