This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krams, M. Articles by Rudolph, P. Search for Related Content PubMed PubMed Citation Articles by Krams, M. Articles by Rudolph, P.

(American Journal of Pathology. 2001;159:1925-1932.)
© 2001 American Society for Investigative Pathology

Regular Articles

Regulation of Telomerase Activity by Alternate Splicing of Human Telomerase Reverse Transcriptase mRNA in a Subset of Neuroblastomas

Matthias Krams^*, Alexander Claviez, Klaus Heidorn^*, Guido Krupp^*, Reza Parwaresch^*, Dieter Harms^* and Pierre Rudolph^*

From the Departments of Pathology^*
and Pediatrics,
University of Kiel, Kiel, Germany

It has been proposed that the regulation of telomerase takes place at the transcriptional level, the expression of the catalytic subunit human telomerase reverse transcriptase (hTERT) being crucial for telomerase activity (TA). Recently, differential splicing of hTERT mRNA has been demonstrated in various tissues during embryonal development, and it has been suggested that only full-length transcripts translate into functionally active telomerase. With this in view, we analyzed the different hTERT transcripts by reverse transcriptase-polymerase chain reaction in neuroblastic tumors and compared the results with the TA, the tumor growth fraction, and the MYCN status. In a series of 38 neuroblastic tumors, high TA and full-length hTERT transcripts were found in nine samples, whereas nine samples showed absence of both enzymatic activity and hTERT transcripts. Interestingly, in another eight samples, low or absent TA coincided with a lack of full-length hTERT transcripts. Eleven samples contained hTERT transcripts with low or undetectable TA and one sample had low TA but no hTERT transcripts. TA correlated with MYCN amplification and was weakly associated with the proliferative activity. Moreover, a significant correlation with tumor progression was observed. Our findings point at a posttranscriptional regulation of TA in a subset of neuroblastic tumors. Because high TA was detected only in tumors with full-length hTERT transcripts, reverse transcriptase-polymerase chain reaction analysis of archival neuroblastic tumor samples might help to appraise the malignant potential in individual cases.

This article has been cited by other articles:

				Y. Fan, Z. Liu, X. Fang, Z. Ge, N. Ge, Y. Jia, P. Sun, F. Lou, M. Bjorkholm, A. Gruber, et al. Differential Expression of Full-length Telomerase Reverse Transcriptase mRNA and Telomerase Activity between Normal and Malignant Renal Tissues Clin. Cancer Res., June 15, 2005; 11(12): 4331 - 4337. [Abstract] [Full Text] [PDF]

				M. Krams, H.-J. Heidebrecht, B. Hero, F. Berthold, D. Harms, R. Parwaresch, and P. Rudolph repp86 Expression and Outcome in Patients With Neuroblastoma J. Clin. Oncol., May 1, 2003; 21(9): 1810 - 1818. [Abstract] [Full Text] [PDF]

				M. Krams, B. Hero, F. Berthold, R. Parwaresch, D. Harms, and P. Rudolph Full-Length Telomerase Reverse Transcriptase Messenger RNA Is an Independent Prognostic Factor in Neuroblastoma Am. J. Pathol., March 1, 2003; 162(3): 1019 - 1026. [Abstract] [Full Text] [PDF]