Hereditary papillary renal carcinoma type I

Pathirage G. Dharmawardana, Alessio Giubellino, Donald P. Bottaro

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)855-868
Number of pages14
JournalCurrent Molecular Medicine
Volume4
Issue number8
DOIs
StatePublished - Dec 2004

Keywords

  • HGF/SF
  • HPRC
  • Missense mutations
  • Renal carcinoma
  • c-Met

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