A NOVEL RENAL-CELL CARCINOMA SUSCEPTIBILITY GENE MAPS ON CHROMOSOME-10 IN THE EKER RAT

Hereditary renal cell carcinoma (RC) in the rat, originally reported b y Eker in 1954, is an example of Mendelian dominant predisposition to a specific cancer in an experimental animal. We previously reported th at this predisposing inherited gene is a tumor suppressor gene fitting Knudson's ''two-hit'' model. This study was designed to map the RC su sceptibility gene in the Eker rat using backcross animals. Our present data clearly show that the RC gene is genetically linked to the prota mine-1 gene (Lod score = 11.65) and the interleukin-3 gene (Lod score = 4.13), both of which are located on the proximal part of rat chromos ome 10. Rat chromosome 10 is currently believed to have no syntenic re lationship to human chromosome 3p, the presumed site of the putative t umor suppressor gene for human RC and the locus of von Hippel Lindau d isease (affected patients develop multiple RCs). Thus, the Eker rat mi ght have a mutation of a novel tumor suppressor gene related to renal carcinogenesis.