1.Clinical cytogeneticist, Department of Clinical Genetics, Academic Hospital Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, the Netherlands
Variants can be assigned which are characterized by augmentation of mitochondria leading to a stronger eosinophilia or granularity, respectively, of the cytoplasm. Spindle-shaped/pleomorphic variants as a result of sarcomatoid transformation can also be found.
Other aberrations frequently found in common RCC are (partial) trisomy of chromosome 5, especially the 5q22-qter segment. Trisomy 12, and 20, and loss of chromosomes 8, 9, 13q, 14q, and structural abnormalities of the long arm of chromosomes 6 and 10 are also found and correlated with progression.
In general, cRCCs are sporadic tumors but also syndromic in patients with the von Hippel-Lindau (VHL) disease (germ line mutations in the VHL tumor suppressor gene assigned to 3p25). Also familial cRCC familial cRCC has been reported. All have in common the presence of abnormalities involving chromosome 3.
Loss of heterozygosity (LOH) and comparative genetic hybridization (CGH) analyses of cRCCs revealed that allelic (interstitial) losses predominantly occur in the chromosome 3p21 region in combination with either 3p25 or 3p13-14, or with both, and these allelic losses were restricted to the cRCC. These results suggest that loss of the 3p21 region is a prerequisite for malignant development of cRCC and indicate that several regions (and thus several genes) on human chromosome 3 contribute to cRCC tumor development.
Until today no tumor suppressor gene responsible for, or at least contributing to, cRCC has been identified -except for VHL-, in the different regions, although many candidate genes have been suggested such as FHIT (fragile histidine triad); TTRC1 (two-three-renal-cancer-1; DUTT1 (deleted in U-twenty twenty); locus NCR-1 (nonpapillary renal cell carcinoma 1) and RASSF1A (RAS association family 1).
The gene in the 3p25 region involved in cRCC development is the von Hippel Lindau (VHL) tumor suppressor gene. Somatic mutations and LOH of the VHL gene were also found in primary sporadic cRCCs. Occurrence of mutations in this gene in both sporadic as well as hereditary forms of cRCC suggests a key role of the VHL gene in oncogenesis. However, VHL is inactivated in only 30-50% of sporadic cRCC, suggesting involvement of another tumor suppressor gene located on 3p.
Loss of heterozygosity on chromosomes 8p or 9p provide prognostic significance in patients with locally advanced cRCC and PTEN/MMAC1 (chromosome 10) inactivation may play a role in the progression of cRCC.
Eva van den Berg ; Stephan Stârkel
Kidney: Clear cell renal cell carcinoma
Atlas Genet Cytogenet Oncol Haematol. 2004-07-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5020/kidney-clear-cell-renal-cell-carcinoma