Loss of heterozygosity at the short arm of chromosome 3 in renal‐cell cancer correlates with the cytological tumour type

Abstract

A majority of renal-cell tumours retain heterozygosity at the short arm of chromosome 3. To investigate possible histopathological differences between tumours with and without such losses, we compared loss of heterozygosity data from 51 tumours with I histological and 2 different cytological classifications of renal-cell tumour. Using the cytological classification of Thoenes et al., we only found tumours with loss of heterozygosity in these authors' clear-cell category. Possibly, only these tumours arise by a mechanism of double loss of a tumour-suppressor gene on 3p, non-clear-cell renal tumours having a different genetic background. Alternatively, deletions may occur in all subtypes, in which case those subtypes in which no LOH is found may also contain deletions too small to be detected with the set of 3p probes we used. A cytogenetic analysis was carried out on 30 of the tumours. Results of molecular and microscopic cytogenetic analyses did not seem to be in agreement in 12 cases. In 6 of these we found allelic losses in tumours showing morphologically normal copies of chromosome 3. Mitotic recombination or loss of one chromosome 3 homologue followed by duplication of the remaining homologue is a likely explanation. The other 6 cases showed microscopic abnormalities of chromosome 3 which were not reflected, or only partly reflected, as allelic losses. These discrepancies are caused either by the limitations of microscopic analysis in exactly determining a breakpoint or tracing a translocated part of a chromosome, or by the failure of molecular analysis to demonstrate LOH if this occurs in only a minority of cells.

Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.

“…We also examined the papillary histologic subtype of renal cell carcinoma for the presence of abnormal methylation of the VHL gene. Loss of the short arm of chromosome 3 (3p) is rare in this type, in sharp contrast to the clear-cell histology where consistent loss of 3p has been found (27)(28)(29)(30)(31)(32). In addition, mutations have not been found in the VHL gene in this subtype (23).…”

Cytogenetic classification of renal cell cancer

“…The nonrandom loss of the Y chromosome in RCC remains obscure and is possibly age-related [14,15]. The most frequent find ing in RCCs of the clear cell type is a deletion or unbalanced translocation involving the short arm of chromosome 3 [16][17][18].…”

Fine Mapping of the Human Renal Oncocytoma-Associated Translocation (5;11)(q35;q13) Breakpoint

“…The t(5;ll)(q35;ql3) has been observed as sole cytogenetic anomaly in at least 3 independent cases and, as such, should be considered as a primary change. Deletion of 3p material that occurs in the majority of renal cell carci nomas [16,17] has not been observed in renal oncocytomas. The presence of mitochondrial DNA alterations has been reported by some investigators [18,19].…”