This second hit involves activation of the myelocytomatosis virus oncogene cellular homolog (c-MYC) pathway, FGFR 3, kirsten rat sarcoma viral antigen (KRAS) and neuroblastoma (N) RAS pathway, and nuclear factor (NF)-κB pathway; loss of function in histone demethylase; activation of toll-like receptor (TLR) signaling; and stimulation from bone marrow microenvironment. Here, FGFR3 is linked to neuroblastoma.