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 t umour types, indicating the presence of at least one tumour suppressor gene on 3p. Previous studies have defined the distal and proximal end s of one critical region to reside between 3p21 and 3p11, and one gene involved in von Hippel-Lindau disease has been identified at 3p25. Ex perimental in vitro data has suggested a negative regulator of telomer ase 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 w as evaluated using the telomeric repeat amplification protocol assay a nd LOH, by analysis of 17 polymorphic microsatellite markers. Twenty-n ine out of 45 tumours (64%) demonstrated telomerase activity and 37 tu mours (82%) showed allelic loss of single or multiple areas of chromos ome 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 telo merase activity was demonstrated (p=0.0031), as well as for three dist al 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 ex pression of telomerase. These genes can encode proteins of importance for senescence and/or immortalisation or have a more direct effect on activation of telomerase.