Abstract
Telomeres and their maintenance by telomerase have been implicated to play an important role in carcinogenesis. As almost all malignant tumors express telomerase (in contrast to normal somatic cells), assessment of its activity has been proposed as a diagnostic and prognostic tool. To test the prognostic value of telomerase in pediatric soft tissue sarcoma (STS), we analyzed telomere length (by telomere restriction fragment analysis), telomerase activity (by modified telomerase repeat amplification protocol assay), and expression of human telomerase reverse transcriptase (hTERT) mRNA (by TaqMan technique) in cell lines of different types of STS from 12 children and adolescents. Telomere length (3.7–9.0 kb) showed a very heterogeneous pattern, independent of subtype of STS or the age of the patients, and it was not associated with expression of hTERT mRNA. In contrast, there was a trend of an association between hTERT and telomerase activity. The three tested cell lines of embryonal rhabdomyosarcomas demonstrated no or low (n = 2) telomerase activity, which was confirmed in two cases by a very low expression of hTERT mRNA. Thus, we suggest that the significant difference (p < 0.01) in the less aggressive clinical behavior of embryonal rhabdomyosarcomas in comparison to other subtypes may be due to differences in telomerase expression. Taken together, our cell line experiments imply that telomerase activity might be a biologic marker for stratification between STS with different clinical prognosis.
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Abbreviations
- TRF:
-
telomere restriction fragment
- TRAP:
-
telomerase repeat amplification protocol
- STS:
-
soft tissue sarcoma
- hTERT:
-
human telomerase reverse transcriptase
- RME:
-
embryonal rhabdomyosarcoma
- RMA:
-
alveolar rhabdomyosarcoma
- PNET:
-
peripheral neuroectodermal tumor
- RT:
-
rhabdoid tumor
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Acknowledgements
The authors thank Mrs. D. Weller and Mrs. K. Simon-Klingenstein for the valuable technical assistance. The cell line MON was kindly provided by Dr. O. Delattre (Paris). We also thank Mrs. Bonilla Torres for secretarial help.
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Supported by the Robert Bosch Foundation Stuttgart, Germany, and by Krebsforschung Schweiz (to B.W.S.).
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Kleideiter, E., Schwab, M., Friedrich, U. et al. Telomerase Activity in Cell Lines of Pediatric Soft Tissue Sarcomas. Pediatr Res 54, 718–723 (2003). https://doi.org/10.1203/01.PDR.0000086901.29111.2A
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DOI: https://doi.org/10.1203/01.PDR.0000086901.29111.2A
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