MYCN pathway and genomic aberrations in neuroblastoma Neuroblastoma is an embryonic tumor derived from the peripheral nervous system. Neuroblastoma is highly heterogeneous in histology, molecular biology and outcome. Genomic aberrations that exist of whole chromosome gains and losses are found in favorable tumors. MYCN (chromosome 2p) is amplified in 20% of neuroblastoma tumors and these tumors follow a particular aggressive course. Other frequent events involve chromosome 1p, 11q and 17q. Interestingly, loss of chromosome 1p and gain of 17q frequently occur in tumors with MYCN amplification.
Previously, we silenced MYCN in a MYCN-amplified cell line, measured expression changes (Affymetrix Array profiling) and integrated these data with neuroblastoma tumors . This resulted in a mycn-157 signature that predicts poor clinical outcome of neuroblastoma patients with and without MYCN amplification. Tissue array analysis of MYCN protein showed that the latter group has increased MYCN protein expression in tumor cells.
Currently we are investigating the involvement of other chromosomal aberrations that occur in neuroblastoma tumors. Using complete genomic sequencing data we can exactly determine the break point regions and identify mutated genes. Silencing (shRNA) and induction of candidate genes in neuroblastoma cell lines will identify genes involved in neuroblastoma development and MYCN stability.

Molecular Biology/Oncology