title: Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients.
abstract: Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas. To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing. Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.
authors.affiliation: Medical Oncology Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Duffy
authors.forename: Tahseen
authors.initials: T
authors.lastname: Al-Saleem
authors.forename: Magdalena
authors.initials: M
authors.lastname: Karbowniczek
authors.forename: David
authors.initials: D
authors.lastname: Ewalt
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Prowse
authors.forename: Elizabeth Petri
authors.initials: EP
authors.lastname: Henske
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008025:Ligases / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014402:Tuberous Sclerosis / Q000150:complications / Q000235:genetics* / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human