[Genetic study of six chromophobic renal carcinomas]

To determine the role of tumor suppressor genes p53 and von Hippel-Lindau (VHL), and the specific loss of chromosomes 1, 2, 3, 6, 10, 13, 17 and 21 in the pathogenesis of Chromophobe Renal Cell Carcinomas (CrRCC).

Renal tumor specimens and normal kidney tissue from 6 patients affected of CrRCC were obtained after radical nephrectomy and immediately snap-frozen. PCR-SSCP analysis for mutations of p53 (exons 5-8) and VHL genes was performed in all cases. All of the positive cases in SSCP analysis were further characterized by direct sequencing. Inactivation by VHL methylation were searched by Southern blot analysis. Microsatellite analysis using several markers covering both arms of chromosomes 1, 2, 6, 10, 13 and 17, as well as 3p and 21q, was performed to investigate specific loss of these chromosomes.

Mutations of p53 were detected in 2 (33%) of the 6 CrRCCs, showing both tumors loss of heterocigosity (LOH) on 17p. VHL mutations and inactivation by methylation were not detected in any tumor. In 5 (83.3%) of the 6 CrRCCs, microsatellite analysis showed LOH at every informative marker on all the regions tested except 3p. Retention of heterozigosity on 3p was present in all cases.

Mutations of p53 in CrRCCs are more frequent (33% in our series) than in clear cell renal cell carcinomas (< 2% in most series). Despite 65-75% of clear cell RCCs show VHL mutations (60%) and inactivation by methylation (5-20%), no CrRCC in our series showed these alterations. LOH in the specific chromosomes tested (1, 2, 6, 10, 13, 17 and 21) confirm cytogenetic findings that characterize CrRCCs (specific combinations of multiple chromosomal losses). Our results, similar to those reported by other authors, confirm that CrRCC is not only a histologic fenotype, but also a distinctive genotype from other RCCs. The specific combination of chromosomal losses allows a quick and easy diagnostic of this kind of neoplasms with a simple technique of microsatellite analysis.