GENETIC ALTERATIONS IN SPORADIC RENAL-CELL CARCINOMA - MOLECULAR ANALYSES OF TUMOR-SUPPRESSOR GENE HARBORING CHROMOSOMAL REGIONS 3P, 5Q, AND 17P

On a genetic level, renal-cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 (3p), which suggests the inactivation of a tumor suppressor gene. One tumor suppressor gene at 3p, the von Hippel-Lindau disease gene, is implicated in tumor develop ment of a whole spectrum of hereditary neoplasms, including renal-cell carcinoma. It is not clear whether the same tumor suppressor gene acc ounts for all, i.e., hereditary and sporadic, renal-cell carcinomas. A nalysis of 28 patients with sporadic renal-cell carcinomas for loss of heterozygosity was performed at chromosomal regions that contain know n tumor suppressor genes so as to assess their potential involvement d uring renal tumorigenesis. We focused on chromosome 3p because it cont ains the von Hippel-Lindau (VHL) disease gene, on 5q because it harbor s tumor suppressor genes involved in colorectal carcinoma, and on 17p because it includes a tumor suppressor gene involved in breast, colon, and lung carcinoma. Loss of alleles at 3p affected 96% of the evaluab le patients, with frequencies being highest in the VHL region in 3p25- 26 and at loci in 3p2l. These data confirm the importance of a 3p defe ct early during tumorigenesis; however, the question as to the existen ce of a second renal-cell carcinoma gene remains unresolved. Changes a t 5q were 53% and those at 17p were 35%, suggesting that these loci ma y not contribute to the initiation of the disease but rather may repre sent accumulating genetic defects associated with progression and mali gnancy.