GENETIC-ANALYSIS OF 2 CASES OF CLEAR-CELL RENAL-CANCER IN 2 SISTERS

Two sisters affected with renal cell carcinoma (RCC) is an extremely r are 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 par t of 5q. The 5q breakpoints were similar, but the breakpoints at 3p ap peared to differ. Allelic imbalance analysis supported our observation s. Microsatellite analysis revealed that both sisters inherited differ ent chromosome 3 parental alleles. For chromosome 5, 3 different haplo types could be deduced, but the chromosome 5 alleles overrepresented i n 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 th e chance that 2 sisters develop sporadic RCC is very low, in the prese nted case it is probably coincidental or related to another genetic pr edisposition. Int. J. Cancer 77:494-497, 1998. (C) 1998 Wiley-Liss, In c.