[Analysis of kidney tumors in trichloroethylene exposed workers by comparative genomic hybridization and DNA sequence analysis]

Abstract

Environmental and occupational mutagens such as chemical agents are suspected to be involved in cancer development. However, a direct link between carcinogen exposure and genetic alterations has been established only in a few examples. Carcinogen involvement in renal cell carcinoma (RCC) was recently supported by reports of an increased frequency of RCC among workers exposed to Trichloroethylene (TRI) in Germany. The aim of this study was to evaluate the phenotype and the genotype of renal tumors in occupationally TRI-exposed patients. Sporadic RCCs from TRI nonexposed patients served as control. Normal and renal tumor tissues from 12 patients with occupational histories of solvents and TRI exposure were histologically analyzed. Comparative Genomic Hybridization (CGH) was used to screen for genomic alterations along all chromosomal arms. Tumor DNA was analyzed for mutations of the von Hippel-Lindau gene (VHL) on 3p25.5 by PCR and sequencing analyses. The histological analysis revealed 9 clear cell (75%), 2 papillary RCC (18%) and 1 oncocytoma (8%). In clear cell RCC, DNA losses were frequently observed on 3p (66%), 6q (56%), 9p and 4q (44% each) and 2q (33%). DNA gains were detected on 9q, 17 (33% each) and 5q (22%). DNA gains were identified on chromosome 7 and 17 in papillary RCC. Four VHL gene mutations were found in three clear cell RCC (33%) with 3p loss. Comparisons of these results with data obtained from sporadic RCC revealed no unique phenotype, genotype or mutation pattern in the VHL gene of renal tumors after TRI exposure. Therefore, further studies on the relevance of dose and exposure time for the nephrocarcinogenic effect of TRI are indicated.