ON TELOMERE SHORTENING IN SOFT-TISSUE TUMORS

Purpose: Specific simple DNA repeats occur at the telomeric ends of ma mmalian chromosomes. Loss of (G + C)-rich repeats can result in geneti c instability, associated with tumorigenesis. So far, data on telomere shortening have not been available for different types of soft-tissue tumors. Methods: Using tumor material and the blood of the correspond ing patient, high-molecular-mass DNA was prepared by digestion with pr oteinase K and extraction with phenol/chloroform. A 10-mu g sample of DNA was digested with the restriction enzyme HinfI. DNA fragments were separated in a 0.7% agarose gel, and in-gel hybridization was perform ed with the telomere-specific repeat probe (TTAGGG)(3). Results: Short ening of the telomere repeat was observed in 14/30 soft-tissue tumors; 5 tumors showed elongated telomere repeats, whereas the telomeres app eared unchanged in 11 tumors. Decreased telomere repeat length correla ted with advanced age, DNA ploidy. and a higher proliferation index. T here was no association between telomere repeat length and tumor grade . Interestingly, in contrast to other entities, all malignant schwanno mas and leiomyosarcomas showed significantly reduced telomere lengths. An explanation for the telomere heterogeneity in liposarcomas may inc lude differential telomerase reactivation in well and poorly different iated tumors. Conclusions: Telomere shortening is frequent but not a u niform phenomenon in different types of soft-tissue tumor. Studies on telomerase activity should be performed in the same cohort of sarcomas .