In Situ Analysis of Telomerase RNA Gene Expression as a Marker for Tumor Progression

Lung cancer is common in men and women, has a very poor prognosis, and is therefore a major cause of premature mortality. As such, any prospects for improved therapy are of great significance ( 1 – 4 ). The promise of telomerase as a therapeutic target is now close to realisation with extremely encouraging preclinical studies aimed at the RNA component (hTERC) of telomerase ( 5 – 11 ). The rational integration of telomerase therapeutics into clinical trials will therefore require tumors to be well characterized for hTERC expression ( 12 – 14 ). The regulation of telomerase activity is likely to be a complex issue including the transcriptional activity of the telomerase RNA component gene hTERC and the telomerase catalytic component gene (hTERT), and the interaction of telomerase with other telomere associated proteins ( 10 , 15 – 20 ; see Fig. 1 ). The use of telomerase as a diagnostic marker and target for cancer therapy relies on the development of reliable assays and technologies to detect telomeres and telomerase expression ( 14 , 21 – 26 ; see Table 1 ). Molecular techniques can be roughly broken down into two groups, lysate analysis and in situ analysis ( 14 , 23 , 27 ). With lysate methods, tumor biopsies are homogenized and the spatial relationships between tumor cells are destroyed (Southern-blot analysis and polymerase chain reaction [PCR]). This leads to a loss of information on heterogeneity and small subpopulations and presents an averaging of changes.

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