DIFFERENCES IN GENE EXPRESSION AND MOLECULAR PATHWAY REGULATION BETWEEN MYCN AMPLIFIED AND 2P GAIN NEUROBLASTOMA TUMORS

Objective: The malignancy of neuroblastoma (NB) is strongly connected with MYCN oncogene status. The gene expression profile was investigated in three subtypes of NB related to MYCN status (amplification - MNA, 2p gain and normal) in order to identify new candidate genes and to elucidate development of more aggressive forms of this pediatric tumor. Materials and Methods: Human whole genome oligonucleotide expression microarrays were applied in the study. Results: Hierarchical clustering analysis presented two distinct gene expression patterns corresponding to cases with and without MNA. For the first time, the 7 most upregulated genes and the 13 most downregulated genes in the MNA subgroup were selected in comparison to 2p gain tumors. Conclusions: The obtained result demonstrates that MYCN has a significant impact on genome-wide NB gene expression. Increasing MYCN level promotes cell growth and motility while counteracting differentiation and attachment. Interestingly, NB with 2p gain, in comparison to MNA and normal MYCN status, showed a higher expression level of genes involved in cell migration but downregulated genes involved in nervous system development. This finding may indicate that 2p gain tumors have more aggressive behavior with a higher tendency toward metastasis than MNA cases.