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 development of a whole spectrum of hereditary neoplasms, including renal-cell carcinoma. It is not clear whether the same tumor suppressor gene accounts for all, i.e., hereditary and sporadic, renal-cell carcinomas. Analysis of 28 patients with sporadic renal-cell carcinomas for loss of heterozygosity was performed at chromosomal regions that contain known tumor suppressor genes so as to assess their potential involvement during renal tumorigenesis. We focused on chromosome 3p because it contains the von Hippel-Lindau (VHL) disease gene, on 5q because it harbors 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 evaluable patients, with frequencies being highest in the VHL region in 3p25-26 and at loci in 3p21. These data confirm the importance of a 3p defect early during tumorigenesis; however, the question as to the existence of a second renal-cell carcinoma gene remains unresolved. Changes at 5q were 53% and those at 17p were 35%, suggesting that these loci may not contribute to the initiation of the disease but rather may represent accumulating genetic defects associated with progression and malignancy.