The genetic basis of cancer of the kidney

J Urol. 2003 Dec;170(6 Pt 1):2163-72. doi: 10.1097/01.ju.0000096060.92397.ed.


Purpose: The types of epithelial renal tumors are clear cell, types I and II papillary, chromophobe and oncocytoma. We identified the genetic basis of these different types of kidney cancer to provide better methods for early diagnosis of this disease as well as provide the foundation for the development of molecular therapeutic approaches.

Materials and methods: To identify the genetic basis of kidney cancer we studied families with an inherited predisposition to kidney cancer. Families in which 2 or more individuals had kidney cancer underwent a comprehensive evaluation to determine whether they were affected with a hereditary form of renal carcinoma. Genetic linkage analysis was performed to identify the gene for inherited forms of renal carcinoma.

Results: The gene for the inherited form of clear cell renal carcinoma associated with von Hippel-Lindau gene was identified. This gene has been found to be a tumor suppressor gene. A new form of inherited renal carcinoma, hereditary papillary renal carcinoma, was identified. The gene for this condition was identified and found to be the proto-oncogene c-Met. A previously unidentified form of familial renal oncocytoma was found. A familial form of chromophobe renal carcinoma and oncocytoma associated with Birt Hogg Dubé syndrome was found. The gene for this condition was localized on the short arm of chromosome 17 and it has been identified. We studied families with cutaneous leiomyomas, uterine leiomyomas and papillary renal carcinoma. We identified mutations in the fumarate hydratase gene in patients affected with this disorder, namely hereditary leiomyoma renal cell carcinoma.

Conclusions: Kidney cancer used to be considered a single disease. It is now known that there are a number of different types of cancers of the kidney with different histological patterns and different clinical courses that appear to respond differently to therapy. These different types of kidney cancer are caused by different genes, ie they each have a distinct genetic basis. Understanding the molecular pathways of these cancer genes should provide insight into their varying clinical courses and responses to treatment as well as provide the foundation for the development of disease specific molecular therapeutic strategies.

Publication types

  • Review

MeSH terms

  • Carcinoma, Papillary / genetics
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • Genes, Tumor Suppressor
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Leiomyoma / genetics
  • Mutation
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / pathology
  • Pedigree
  • Pheochromocytoma / genetics
  • Proteins / genetics
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-met / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein
  • von Hippel-Lindau Disease / genetics


  • FLCN protein, human
  • Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Proto-Oncogene Proteins c-met
  • VHL protein, human