Loss of heterozygosity at chromosome 3p correlates with telomerase activity in renal cell carcinoma.
Acquired loss of the entire or parts of the short arm of chromosome 3 is a frequent aberration in renal cell carcinoma as well as in other tumour types, indicating the presence of at least one tumour suppressor gene on 3p. Previous studies have defined the distal and proximal ends of one critical region to reside between 3p21 and 3p11, and one gene involved in von Hippel-Lindau disease has been identified at 3p25. Experimental in vitro data has suggested a negative regulator of telomerase activity on chromosome 3. In the present study we investigated the relationship between telomerase activity and loss of heterozygosity (LOH) on 3p in a series of renal cell carcinomas. Telomerase activity was evaluated using the telomeric repeat amplification protocol assay and LOH, by analysis of 17 polymorphic microsatellite markers. Twenty-nine out of 45 tumours (64%) demonstrated telomerase activity and 37 tumours (82%) showed allelic loss of single or multiple areas of chromosome 3p. A significant correlation between LOH of at least one of three markers localised within 4 cM in the region of 3p21.2-3p14.2 and telomerase activity was demonstrated (p=0.0031), as well as for three distal markers within 3 cM at 3p24.3-3p24.1 (p=0.0287). These data suggest the presence of at least two genes with regulatory function on the expression of telomerase. These genes can encode proteins of importance for senescence and/or immortalisation or have a more direct effect on activation of telomerase.
Mehle
C
C
Department of Pathology, Umea University, S-90187 Umea, Sweden.
Lindblom
A
A
Ljungberg
B
B
Stenling
R
R
Roos
G
G
D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics*; D016922:Cellular Senescence / Q000502:physiology; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics*; D019656:Loss of Heterozygosity; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
D019098:Telomerase