DUPLICATION OF AN APPROXIMATELY 1.5 MB DNA SEGMENT AT CHROMOSOME 5Q22INDICATES THE LOCUS OF A NEW TUMOR GENE IN NONPAPILLARY RENAL-CELL CARCINOMAS

Previous karyotyping showed an unbalanced translocation between chromo some 3p11.2-p13 and chromosome 5q22 leading to duplication of chromoso me 5q22-qter region in nonpapillary renal cell carcinomas. In order to determine the breakpoint at chromosome 5q22 at the molecular level, w e have investigated 50 sporadic nonpapillary renal cell carcinomas fro m consecutive nephrectomies and 24 renal cell carcinomas obtained from two patients with von Hippel-Lindau disease. We used seven DNA marker s mapped to and around the APC and MCC genes to detect allelic imbalan ce. We observed a duplication of chromosome 5q sequences in 11 of 23 i nformative sporadic tumours and in 18 of 24 hereditary tumours. We det ermined a breakpoint cluster between the APC and MCC genes at chromoso me 5q22. In addition we have found a partial duplication of the smalle st overlapping region of about 1.5 Mb sequences including the MCC gene in seven tumours without visible alteration of chromosome 5q in the k aryotype. We suggest that this DNA segment harbours a gene or gene clu ster, the altered dosage of which is important for the growth of nonpa pillary renal cell carcinomas.