Nat Commun: "Enhanced subcapajaja" event determines the structure of ecDNA MYCN amplification in neuroblastoma

The amplification of cancer genes is a marker of the cancer genome, which can lead to the overexplification of primary cancer genes and is a key driver of carcinogenic effects.
studies have shown that there are two main forms of redundant gene copies: (i) self-repeating arrays on chromosomes (homogeneity chromosomal regions, HSRs) and (ii) many independent ring DNA molecules (chromosome outer ring DNA, ecDNA).
ecDNA may be produced and amplified in genome recombination events such as chromothripsis.
ecDNA re-integration into chromosomes can lead to amplification in chromosomes and act as a driving force for genomic remodeling.
, however, little is known about the function of the non-coding areas that are co-amplified in ecDNA.
has identified five specific enhancers in neuroblastoma cells that express MYCN, and previous studies have shown that amplification of the MYCN gene is a driving force behind one in six neuroblastomas.
are usually found on highly rearmed ecDNA.
so far, the exact amplification substruct and its rearfuration function have not been clear.
the study, the researchers analyzed the structure of myCN amplifier using short-read sequencing and nanopore sequencing techniques, and analyzed its chromatin spectrometry using ChIP-seq, ATAC-seq, and Hi-C.
two types of MYCN amplifications can be found in neuroblastoma to reveal two different types of amplifications to explain the regulation of MYCN over-expression.
researchers found that the first class of amplifications was always amplified together with near-end enhancers driven by CRC (the epinephrine regulatory circuit).
second class of MYCN amplifier manifests itself as a highly complex structure, lacking critical in-place enhancers, and instead containing far-end chromosome fragments with CRC-driven enhancers.
enhancer co-amplification determines the pattern of MYCN amplifier in general, and this study shows that heterogeneity enhancer hijacking compensates for the in-place absence of gene regulatory elements, and this finding also provides a major explanation for the structural diversity observed during MYCN amplification.
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