Regulation of telomerase activity by alternate splicing of human telomerase reverse transcriptase mRNA in a subset of neuroblastomas

It has been proposed that the regulation of telomerase takes place at the t ranscriptional level, the expression of the catalytic subunit human telomer ase reverse transcriptase (hTERT) being crucial for telomerase activity (TA ). Recently, differential splicing of hTERT mRNA has been demonstrated in v arious 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 compare d the results with the TA, the tumor growth fraction, and the MYCN status. In a series of 38 neuroblastic rumors, high TA and full-length hTERT transc ripts were found in nine samples, whereas nine samples showed absence of bo th enzymatic activity and hTERT transcripts. Interestingly, in another eigh t samples, low or absent TA coincided with a lack of full-length hTERT tran scripts. Eleven samples contained hTERT transcripts with low or undetectabl e TA and one sample had low TA but no hTERT transcripts. TA correlated with MYCN amplification and was weakly associated with the proliferative activi ty. 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 rumors with fu ll-length hTERT transcripts, reverse transcriptase-polymerase chain reactio n analysis of archival neuroblastic tumor samples might help to appraise th e malignant potential in individual cases.