title: Cytogenetic and molecular analysis of early stage renal cell carcinomas in a family with a translocation (2;3)(q35;q21).
abstract: Previously, we described a family with renal cell carcinoma (RCC) and a constitutional balanced t(2;3) (q35;q21). Based on loss of heterozygosity and von Hippel-Lindau (VHL) gene mutation analyses in five tumor biopsies from three patients in this family, we proposed a multistep model for RCC development in which the familial translocation may act as a primary oncogenic event leading to (nondisjunctional) loss of the translocation-derived chromosome 3, and somatic mutation of the VHL gene as a secondary event related to tumor progression. Here, we describe the cytogenetic and molecular analysis of three novel tumors at early stages of development in two members of this family. Again, loss of derivative chromosome 3 was found in two of these tumors and a VHL mutation in one of them. In the third tumor, however, none of these abnormalities could be detected. These results underline our previous notion that loss of derivative chromosome 3 and VHL gene mutation play critical roles in familial RCC. In addition, they show that both anomalies may occur at relatively early stages of tumor development.
authors: Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. d.bodmer@antrg.azn.nl
authors: Danielle
authors: D
authors: Bodmer
authors: Marc
authors: M
authors: Eleveld
authors: Marjolijn
authors: M
authors: Ligtenberg
authors: Marian
authors: M
authors: Weterman
authors: Adrian
authors: A
authors: van der Meijden
authors: Marianne
authors: M
authors: Koolen
authors: Christien
authors: C
authors: Hulsbergen-van der Kaa
authors: Arie
authors: A
authors: Smits
authors: Dominique
authors: D
authors: Smeets
authors: Ad
authors: A
authors: Geurts van Kessel
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008025:Ligases / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D010375:Pedigree; D017354:Point Mutation; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human