Cytogenetic and molecular analysis of early stage renal cell carcinomas in a family with a translocation (2;3)(q35;q21).
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.
Bodmer
Danielle
D
Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. d.bodmer@antrg.azn.nl
Eleveld
Marc
M
Ligtenberg
Marjolijn
M
Weterman
Marian
M
van der Meijden
Adrian
A
Koolen
Marianne
M
Hulsbergen-van der Kaa
Christien
C
Smits
Arie
A
Smeets
Dominique
D
Geurts van Kessel
Ad
A
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
D004273:DNA, Neoplasm; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human