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Rearrangements of minisatellites in the human telomerase reverse transcriptase gene are not correlated with its expression in colon carcinomas

Oncogene volume 20, pages 2600–2605 (2001)Cite this article

Abstract

Telomerase activation is crucial in human carcinogenesis. The limiting component of telomerase, the catalytic subunit (hTERT), is undetectable in normal somatic cells but present in most tumor cells, including the earliest stages of colon carcinoma. The mechanisms involved in the differential expression in normal and tumor cells are not understood. In normal cells hTERT expression is shut down by a repressor, and upregulation could be a consequence of cis-acting changes in the hTERT gene, making it resistant to repression. We have identified a polymorphic and a monomorphic minisatellite in the second intron of the hTERT gene, and polymorphic one in intron 6. The polymorphic minisatellite in intron 2 contains binding sites for c-Myc, which has been shown to upregulate hTERT transcription. Screening colon carcinoma DNAs for rearrangements of hTERT minisatellites we detected no changes in 33 samples from tumors, most of which express hTERT. This indicates that size rearrangements of the hTERT minisatellites are not required for telomerase expression in colon carcinomas. Minor changes and one LOH were seen in five tumors.

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Acknowledgements

We thank Mario Amacker and Anne-Lyse Ducrest for the hTERT genomic clone and discussions, volunteers from the Mathieu and Nabholz families for blood and Curzio Rüegg for taking blood samples. Patricia Corthésy provided technical help with the Southern blots and Anna Englezou the DNA samples from SV40 transformed fibroblasts. This work has been supported by grants from the Swiss National Science Foundation (M Nabholz and J Lingner), the Swedish Cancer Society (R Palmqvist, R Stenling, and G Roos), the fifth framework programme from the European Union (J Lingner and G Roos; J Lingner via the Bundesamt für Bildung und Wissenschaft, Bern); and New South Wales Cancer Council (R Reddel).

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Authors and Affiliations

  1. Institute for Experimental Cancer Research, Epalinges, CH-1066, Switzerland

    Henrietta Szutorisz, Joachim Lingner & Markus Nabholz

  2. Department of Medical Biosciences, Pathology, Umeå University, Umeå, SE-901 87, Sweden

    Richard Palmqvist, Göran Roos & Roger Stenling

  3. Division of Medical Genetics, CHUV, Lausanne, CH-1011, Switzerland

    Daniel F Schorderet

  4. Children's Medical Research Institute, Westmead, AU-2145, Australia

    Roger Reddel

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  1. Henrietta Szutorisz
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Szutorisz, H., Palmqvist, R., Roos, G. et al. Rearrangements of minisatellites in the human telomerase reverse transcriptase gene are not correlated with its expression in colon carcinomas. Oncogene 20, 2600–2605 (2001). https://doi.org/10.1038/sj.onc.1204346

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