F. Genetics

Clear cell renal cell carcinoma Clear cell RCC are of sporadic or hereditary origin, the latter are part of the von Hippel-Lindau syndrome. They have in common the complete or partial loss (p-segment) of chromosome 3 or molecular abnormalities on the short arm of chromosome 3. This results in the loss of one or more tumor suppressor genes. Besides the VHL gene on 3p25, genes on the regions of 3p21 and 3p12- 4 are involved alone or in combination. Increasing dedifferentiation (GI > Gill) leads to an overexpression of chromosome 7, 5q, and 10, whilst metastasis is associated with an amplification of 1q. Chromophil renal cell carcinoma Chromophil RCC have characteristic chromosomal aberrations like + 7 I +17, and -Y. Tumor progression is associated with an overexpression of chromosome 16, 12, 3q, and in the case of sarcomatoid transformation, of chromosome 10. The finding of an additional loss of the 3p21 region in some chromophil RCC might lead to the development of the more malignant clear cell RCC, which reflects the close relationship of these tumors mentioned above. Renal oncocytoma Renal oncocytomas are heterogeneous cytogenetically. One group is characterized by a reciprocal translocation t(5;11)(q35;q13). This breakpoint involves genes responsible for enzymes of the respiratory chain in the mitochondrial membranes. A second group lacks the chromosomes -1 and -yand is often found with telomeric associations. Chromophobe renal cell carcinoma Chromophobe RCC have the greatest loss of chromosomal material known in tumor cytogenetics. A typical finding is multiple monosomies (-1, -2, -6, -10, -13, -17, -21, and -Y), which have been confirmed by classical cytogenetics, FISH analysis and comparative genomic hybridization studies. This chromosomal pattern resembles in part the findings in renal oncocytomas and is a strong evidence for a cytogenetic relationship too. Collecting duct carcinoma Cytogenetics of this rare tumor entity are inconsistent up to now. While one paper reports losses of chromosomes -1, -6, -14, -15, and -22, our results point to aberrations of 8p- and -13. Similar chromosomal abnormalities are never found in any kidney tumor. Intra-renal urothelial carcinoma Intra-renal urothelial carcinoma are cytogenetically similar to those of the urinary tract. They express complex chromosomal aberrations like -9, -17p, +8q, -13q, -18q, and +17q. Neuroendocrine tumors of the kidney Up to now there are no reliable cytogenetic data of this special kidney tumor type. Numerical and structural aberrations of chromosome 13 seem to be involved yet. Metanephric adenoma There is only one karyogram published, and it shows normal chromosomes. Our CGH data on this tumor do not demonstrate any numerical or structural chromosomal aberration. Conclusion: The cytogenetic and molecular genetic results confirm the new morphological classification of epithelial kidney tumors.