TELOMERASE ACTIVITY IN SKELETAL SARCOMAS

Background: Telomerase is a ribonucleoprotein that adds TTAGCG nucleot ide repeats onto the ends of eukaryotic chromosomes to maintain telome re integrity. Somatic cells do not express telomerase and stop dividin g when the chromosomal ends are shortened critically after many cell d ivisions. Immortal cell lines and cancer cells apparently have telomer ase activity that contributes to an unlimited number of cell cycles. T he purpose of our study is to investigate whether telomerase activity is expressed in primary malignant turners of the skeletal system when compared to adjacent normal tissue. Methods: Fresh tumor and normal ti ssue was collected from 14 patients (10 males, 4 females; age range, 8 to 76 years) and protein extraction performed. The tumors included se ven osteosarcomas (three examined before and after chemotherapy), two chondrosarcomas, two spindle cell tumors, one hemangiopericytoma, one chordoma, and one adamantinoma. Telomerase activity was analyzed by us ing a highly sensitive polymerase chain reaction (PCR)-based assay (te lomere repeat amplification protocol [TRAP]). Results: Telomerase acti vity was found in 8 of 14 sarcoma patients (57%) using the TRAP assay. Compared to HeLa cell extract (positive control), telomerase activity in the tumor specimen ranged from 0 (in osteosarcoma) to 11.7% (in he mangiopericytoma). There was variation in the number of telomeric repe ats generated by telomerase. At least five telomeric bands (e.g. 50, 5 6, 62, 68, 74 bp) in a ladder pattern had to be present before telomer ase activity was considered positive in our analysis. Conclusions: Tel omerase activity may be an oncogenic sustaining event helping to maint ain the transformed phenotype seen in malignant tumors of the bone. Th e degree of telomerase activity varies among skeletal malignancies, bu t was less than that observed in HeLa cells. The majority of osteosarc omas showed no telomerase activity.