Mutational scenario #1 was enriched in high-risk MYCN-amplified neuroblastomas and was defined by footprints of DNA damage by ROS (SBS18), replication slippage (ID1/ID2), replication stress (CX5/CX11), and SV-based signature SV3/R6b, association with clustered SVs, and focal oncogene amplification in the form of ecDNA. Here, MYCN is linked to neuroblastoma.