Differential Gene Expression Profiles between Neuroblastomas with High Telomerase Activity and Low Telomerase Activity

Purpose: Neuroblastoma shows remarkable heterogeneity, resulting in favorable or unfavorable outcomes. The authors previously reported that high levels of telomerase activity correlated with unfavorable tumors, and telomere shortening without telomerase activity correlated with tumor regression. To identify the genes responsible for the biological characteristics of neuroblastoma, the authors applied microarray techniques. Methods: Mixtures of total RNAs extracted from 10 neuroblastoma tissues with high and 10 with low telomerase activity were labeled with Cy3 or Cy5 by reverse transcriptase reaction, respectively, and hybridized with our original microarrays prepared with a cDNA library of human fetal brain. Results: Expression of 63 genes including MYCN, hTERT, HSPCA, and cell cycle-related proteins was found to be increased in neuroblastomas with high telomerase activity, whereas another 46 genes, including neural differentiating genes, were detected as highly expressed in tumors with low telomerase activity. Conclusions: The expression profiling data indicated clusters of upregulated and downregulated genes tumors with high or low telomerase activity. The genes involved in differentiation/growth arrest of tumor cells were closely related to low telomerase activity in neuroblastoma. The genes overexpressed in tumors with high telomerase activity, including cell-cycle-related genes and transcriptional factors, would be candidates for novel prognosis-predicting factors as well as new therapeutic targets in aggressive neuroblastomas.