Hereditary papillary renal carcinoma type I

Curr Mol Med. 2004 Dec;4(8):855-68. doi: 10.2174/1566524043359674.


Germline missense mutations in the tyrosine kinase domain of the hepatocyte growth factor/scatter factor (HGF/SF) receptor, c-Met, are thought to be responsible for hereditary papillary renal carcinoma (HPRC) type 1, a form of human kidney cancer. In addition to extensive linkage analysis of HPRC families localizing the HPRC type 1 gene within chromosome 7, the demonstration that individual c-Met mutations reconstituted in cultured cells display enhanced and dysregulated kinase activity, and confer cell transformation and tumorigenicity in mice, solidifies this conclusion. Our prior knowledge of HGF/SF biology and c-Met signaling enabled rapid progress in unraveling the molecular pathogenesis of HPRC type 1, and in laying the framework for the development of novel therapeutics for the treatment of this cancer. At the same time, the study of HPRC type 1 has refined our appreciation of the oncogenic potential of c-Met signaling, and challenges our current understanding of HGF/SF and c-Met function in health and disease.

Publication types

  • Review

MeSH terms

  • Carcinoma, Papillary / classification
  • Carcinoma, Papillary / genetics*
  • Cell Line, Tumor
  • Humans
  • Kidney Neoplasms / classification
  • Kidney Neoplasms / genetics*
  • Mutation
  • Proto-Oncogene Proteins c-met / genetics*


  • Proto-Oncogene Proteins c-met