Telomerase activity in neuroblastoma: is it a prognostic indicator of clinical behaviour?
Neuroblastomas show remarkable biological heterogeneity, resulting in favourable prognosis or unfavourable prognosis due to aggressive growth despite multimodal therapy. Recently, we proposed that aggressive tumours express telomerase at a high level while the favourable tumours lack or have low telomerase expression. To evaluate the correlation between telomerase activity and other biological characteristics reported as prognostic markers (MYCN gene amplification, loss of heterogeneity (LOH) in the short arm of chromosome 1, trk-A expression, Ha-ras p21 expression, and DNA ploidy), we investigated these biological features in 105 untreated neuroblastomas. In these cases, 23 showed high telomerase activity, 78 showed low activity, and telomerase activity was undetectable in 4 cases. Most tumours with genetic alterations (MYCN amplification or 1p32 LOH) showed high telomerase activity. Most tumours with low or undetectable activity were aneuploid, and showed trk-A and Ha-ras expression. Three of the four tumours with undetectable telomerase activity regressed. In 2 of the tumours with low telomerase activity, the residual tumours maturated and showed repression of telomerase activity. Thus, the level of telomerase activity correlated with other genetic alterations and/or gene expression and may be a useful prognostic indicator in neuroblastoma.
Hiyama
E
E
Department of General Medicine, Hiroshima University School of Medicine, Japan.
Hiyama
K
K
Ohtsu
K
K
Yamaoka
H
H
Ichikawa
T
T
Shay
J W
JW
Yokoyama
T
T
D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005784:Gene Amplification; D011905:Genes, ras; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009857:Oncogenes / Q000235:genetics; D011003:Ploidies; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure
D009363:Neoplasm Proteins; D019098:Telomerase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)