ANALYSIS OF 3P ALLELIC LOSS IN PAPILLARY AND NONPAPILLARY RENAL-CELL CARCINOMAS - CORRELATION WITH TUMOR KARYOTYPES

Nonpapillary renal cell carcinomas (RCCs) are characterized by deletio ns of the short arm of chromosome 3 (3p) and papillary RCCs by increas ed numbers of selected chromosomes. Although recent molecular genetic studies have reported some papillary RCCs to show loss of heterozygosi ty (LOH) on 3p, a 3p deletion has not been demonstrated in a papillary RCC by karyotype analysis. To investigate this apparent discrepancy b etween molecular methods and chromosomal changes in the genetic evalua tion of RCC, a series of 13 papillary and nonpapillary RCCs was invest igated for 3p LOH by PCR-based restriction fragment length polymorphis m (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 alle les was found in 8 of 10 nonpapillary RCCs. The region of overlapping deletion was 3p14-p21, and in six cases the deletion involved 3pter lo ci. One papillary RCC displayed 3p and 3q LOH, but the tumor had two m orphologically normal chromosomes 3 and several trisomies. This indica ted 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 alle les to homozygosity, but the karyotype change, consisting of an increa sed number of whole chromosomes and an absence of a structural chromos ome 3 abnormality, is regarded as being more characteristic of papilla ry than nonpapillary RCC.