Telomerase activity in melanoma and non-melanoma skin cancer

Telomeres are specialized structures consisting of repeat arrays of TTAGGG( n) located at the ends of chromosomes. They are essential for chromosome st ability and, in the majority of normal somatic cells, telomeres shorten wit h each cell division. Most immortalized cell lines and tumours reactivate t elomerase to stabilize the shortening chromosomes. Telomerase activation is regarded as a central step in carcinogenesis and, here, we demonstrate tel omerase activation in premalignant skin lesions and also in all forms of sk in cancer. Telomerase activation in normal skin was a rare event, and among 1.6 samples of normal skin (one with a history of chronic sun exposure) 12 .5% (2 out of 16) exhibited telomerase activity. One out of 16 (6.25%) beni gn proliferative lesions, including viral and seborrhoeic wart samples, had telomerase activity. In premalignant actinic keratoses and Bowen's disease , 42%(11 out of 26) of samples exhibited telomerase activity. in the basal cell carcinoma and cutaneous malignant melanoma (CMM) lesions, telomerase w as activated in 77% (10 out of 13) and 69% (22 out of 32) respectively. How ever, only 25% (3 out of 12) of squamous cell carcinomas (SGG) had telomera se activity. With the exception of one SGG sample, telomerase activity in a positive control cell line derived from a fibrosarcoma (HT1080) was not in hibited when mixed with the telomerase-negative SCC or CMM extracts, indica ting that, overall, Tag polymerase and telomerase inhibitors were not respo nsible for the negative results. Mean telomere hybridizing restriction frag ment (TRF) analysis was performed in a number of telomerase-positive and ne gative samples and, although a broad range of TRF sizes ranging from 3.6 to 17 kb was observed, a relationship between telomerase status and TRF size was not found.