title: Germline and somatic c-met mutations in multifocal/bilateral and sporadic papillary renal carcinomas of selected patients.
abstract: Papillary renal carcinoma (PRC) comprises about 10% of all kidney epithelial tumors. Familiar/hereditary papillary renal carcinomas (HPRCs) have been described, but the majority of cases seem to be sporadic. HPRC is characterized by the predisposition to develop bilateral, multifocal renal tumors. Activating mutations in the tyrosine kinase domain (TK) of the hepatocyte growth factor (HGF) receptor, c-met, have been identified in both hereditary and sporadic PRC. The main aim of this study was to examine a family with no history of PRC in which the proband was a female patient affected by multiple and bilateral PRC at early onset. DNA mutation analysis has been performed by direct sequencing of exons 14-21 of c-met gene which include the TK domain. The proband displayed the germline c-met missense mutation g.3522G--> A in exon 16. Two other family members were found to carry the same mutation. The mutation analysis extended to 15 selected patients, allowed to identify the first case of an Italian patient affected by PRC displaying the somatic missense mutation g.3997 T-->C curved arrow C located in exon 19 of c-met. The mutation frequency of the selected-based population of PRC patients in this report was 12.5%. Furthermore, the phosphorylated c-met expression detected by immunohistochemistry in PRCs with germline/somatic or no c-met mutation, supports the concept that c-met activation may occur in PRC oncogenesis by c-met mutations and/or c-met over-expression.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, IDET Centre of Excellence, University of Brescia, I-Brescia 25123, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salvi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Marchina
authors.forename: Anna
authors.initials: A
authors.lastname: Benetti
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Petro
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
mesh_terms: D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism
chemical_list: D019859:Proto-Oncogene Proteins c-met