LOCALIZATION OF TUMOR-SUPPRESSOR LOCI ON CHROMOSOME-9 IN PRIMARY HUMAN RENAL-CELL CARCINOMAS

To investigate the potential lass of tumor suppressor gene loci on chr omosome 9 in human renal cell tumorigenesis we analyzed 42 paired norm al and tumor DNAs with 18 polymorphic microsatellite markers spanning this chromosome. Fourteen of 42 (33%) tumors showed partial or complet e deletion of chromosome 9. Deletion mapping provided evidence for the presence of a suppressor locus on both the short and long arm of chro mosome 9. Homozygous deletion at 9p21-22 in one renal tumor and a sele ctive deletion of distal 9q in another tumor localized the critical re gions. The CDNK2/p16 gene was further investigated as a candidate supp ressor locus on 9p21-22 by multiplex PCR, Southern analysis, and exon sequencing. We found no additional cases of homozygous deletion nor an y rearrangements or point mutations of CDKN2/p16. This is the first re port of 9p loss of heterozygosity, homozygous deletion of 9p21-22 and selective deletion of 9q in primary renal cell carcinomas. Understandi ng the molecular genetic basis of renal cell progression will require the isolation and characterization of additional tumor suppressor gene s on chromosome 9.