Analysis of 3p allelic loss in papillary and nonpapillary renal cell carcinomas. Correlation with tumor karyotypes.

Nonpapillary renal cell carcinomas (RCCs) are characterized by deletions of the short arm of chromosome 3 (3p) and papillary RCCs by increased numbers of selected chromosomes. Although recent molecular genetic studies have reported some papillary RCCs to show loss of heterozygosity (LOH) on 3p, a 3p deletion has not been demonstrated in a papillary RCC by karyotype analysis. To investigate this apparent discrepancy between molecular methods and chromosomal changes in the genetic evaluation of RCC, a series of 13 papillary and nonpapillary RCCs was investigated for 3p LOH by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis and for 3p and 3q LOH by microsatellite analysis. Karyotypes were obtained in six cases. Loss of 3p but not of 3q alleles was found in 8 of 10 nonpapillary RCCs. The region of overlapping deletion was 3p14--p21, and in six cases the deletion involved 3pter loci. One papillary RCC displayed 3p and 3q LOH, but the tumor had two morphologically normal chromosomes 3 and several trisomies. This indicated that nondisjunction of a chromosome from one parent compensated a whole chromosome loss from the other parent during tumor development. LOH in this papillary RCC constituted a reduction of chromosome 3 alleles to homozygosity, but the karyotype change, consisting of an increased number of whole chromosomes and an absence of a structural chromosome 3 abnormality, is regarded as being more characteristic of papillary than nonpapillary RCC.