TELOMERASE ACTIVITY IN NEUROBLASTOMA - IS IT A PROGNOSTIC INDICATOR OF CLINICAL BEHAVIOR

Neuroblastomas show remarkable biological heterogeneity, resulting in favourable prognosis or unfavourable prognosis due to aggressive growt h despite multimodal therapy. Recently, we proposed that aggressive tu mours express telomerase at a high level while the favourable tumours lack or have low telomerase expression. To evaluate the correlation be tween telomerase activity and other biological characteristics reporte d as prognostic markers (MYCN gene amplification, loss of heterogeneit y (LOH) in the short arm of chromosome 1, trk-A expression, Ha-ras p21 expression, and DNA ploidy), we investigated these biological feature s in 105 untreated neuroblastomas. In these cases, 23 showed high telo merase activity, 78 showed low activity, and telomerase activity was u ndetectable in 4 cases. Most tumours with genetic alterations (MYCN am plification or 1p32 LOH) showed high telomerase activity. Most tumours with low or undetectable activity were aneuploid, and showed trk-A an d Ha-ras expression. Three of the four tumours with undetectable telom erase activity regressed. In 2 of the tumours with low telomerase acti vity, the residual tumours maturated and showed repression of telomera se activity. Thus, the level of telomerase activity correlated with ot her genetic alterations and/or gene expression and may be a useful pro gnostic indicator in neuroblastoma. (C) 1997 Elsevier Science Ltd.