title: Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas.
abstract: We analyzed 47 primary sporadic human renal cell carcinomas (39 clear cell and 8 non-clear cell) for mutations of the von Hippel-Lindau (VHL) tumor suppressor gene using the polymerase chain reaction and single strand conformational polymorphism analysis of DNA. All of the positive cases in single strand conformational polymorphism analyses were further characterized by direct sequencing. Somatic mutations were detected in 22 (56%) of 39 clear cell renal carcinomas including 15 deletions, 3 insertions, 3 missense mutations, and 1 nonsense mutation. Nineteen of these mutations predicted to produce truncation of the VHL protein. These mutations mainly occurred in the last one-third region of exons 1, 2, and 3. In addition, loss of heterozygosity of the VHL gene was observed in 16 (84%) of 19 informative clear cell renal carcinomas. No somatic mutations were detected in 8 non-clear cell carcinomas. These results show that the VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinomas, especially in the clear cell subtype renal cell carcinoma. Clear cell carcinoma might be distinguished from other pathological types of renal cell carcinomas by molecular genetic techniques.
authors.affiliation: Department of Urology, Yokohama City University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shuin
authors.forename: K
authors.initials: K
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Torigoe
authors.forename: T
authors.initials: T
authors.lastname: Kishida
authors.forename: Y
authors.initials: Y
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Hosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Nagashima
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
authors.forename: F
authors.initials: F
authors.lastname: Latif
authors.forename: B
authors.initials: B
authors.lastname: Zbar
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction