Supplementary Material for: Integrated Cytogenetic and High-Resolution Array CGH Analysis of Genomic Alterations Associated with <i>MYCN</i> Amplification

Amplification of oncogenes and closely linked flanking genes is common in some types of cancer and can be associated with complex chromosome rearrangements and/or co-amplification of non-syntenic chromosomal regions. To better understand the etiology and structural complexity of focal <i>MYCN</i> amplicons in human neuronal cancer, we investigated the precise chromosomal locations of high copy number genomic regions in <i>MYCN</i> amplified cell lines. An integrated cytogenetic map of the <i>MYCN</i> amplicon was created using high-resolution array CGH, spectral karyotyping (SKY), multi-color banding (mBAND), and fluorescence in situ hybridization (FISH) in 4 human neuronal tumor cell lines. The evidence of complex intra- and inter-chromosomal events, providing clues concerning the nature of the genomic mechanisms that contributed to the process of <i>MYCN</i> amplification, was observed. The presence of multiple co-amplified syntenic or non-syntenic sequences in the <i>MYCN</i> amplicon is quite intriguing. <i>MYCN</i> is usually centrally located in the amplicon; however, the structure and complexity of the amplicons were highly variable. It is noteworthy that clusters of unstable repetitive regions characterized by CNV sequences were present throughout the regions encompassed by <i>MYCN</i> gene amplification, and these sequences could provide a mechanism to destabilize this region of the genome. Complex structural rearrangements involving genomic losses and gains in the 2p24 region lead to <i>MYCN</i> amplification and that these rearrangements can trigger amplification events.



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