Descriptive and functional analysis of amplified genome regions in primary human neuroblastoma and human neuroblastoma cell lines

Introduction: A strong predictor of poor prognosis in neuroblastoma (NB) is the amplification of the oncogene MYCN. MYCN is a transcription factor that regulates target genes, which affect processes like cell cycle, differentiation and apoptosis.

Methods and results: As a model system for gene amplification we use the dhfr-gen, which is amplified in cells in response to exposure to methotrexat (MTX). The activation of MYCN in the NB cell line SHEP-MYCN-ER leads to an enhanced formation of MTX-resistant cell clones coinciding with an increased genomic instability caused by MYCN. The structure of the dhfr-amplicons of the MTX-resistant cell clones will be characterized using microarray methods. Also, the epigenetic nature of MYCN-amplicons in NB cell lines will be examined using ChIP-array-technology.

Conclusion: Understanding the mechanism of amplification might be an important issue for future therapies.