title: VHL gene alterations in Italian patients with isolated renal cell carcinomas.
abstract: Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of the kidney and belongs to the few human tumors known to develop from mutations of the VHL tumor suppressor gene. VHL germline mutations are associated with hereditary ccRCCs in VHL disease. However, somatic VHL gene defects may also occur in sporadic ccRCCs. In this study, we analyzed the frequency and the spectrum of VHL gene alterations in 35 Italian patients with sporadic renal cell carcinoma (RCC). Tumor-specific intragenic VHL pathogenic mutations were detected in 38% (11/29) of the ccRCC patients and 33% (2/6) of the patients with other types of RCC. One novel 18-bp in-tandem duplication and 4 previously unreported nucleotide changes in the VHL gene were described. Microsatellite analysis showed loss of heterozygosity for at least 1 informative marker in 43% (9/21) of the ccRCCs and 50% (3/6) of the non-ccRCCs; 5 of the 13 tumors (38%) harboring VHL gene alterations also had loss of heterozygosity for at least 1 microsatellite marker. Our results confirm that somatic inactivation of the VHL gene may play a pivotal role in the tumorigenesis of sporadic ccRCCs in Italian patients and suggests that mutation analysis of the VHL gene may be helpful for discriminating sporadic, VHL-gene-related ccRCCs from those related to VHL disease.
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Foggia, Italy. l.muscarella@operapadrepio.it
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.forename: Leonardo
authors.initials: L
authors.lastname: D'Agruma
authors.forename: Annamaria
authors.initials: A
authors.lastname: la Torre
authors.forename: Maddalena
authors.initials: M
authors.lastname: Gigante
authors.forename: Michelina
authors.initials: M
authors.lastname: Coco
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carrieri
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Elena
authors.initials: E
authors.lastname: Ranieri
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D018807:Polymorphism, Single-Stranded Conformational; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000473:pathology
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human