Multicellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53
Fig 9
Sensitivity analysis evaluating 1000 MYCN-amplified (MA) clones with different gene expression profiles.
(A) The violin plots present how the expression levels of each gene are distributed over the profiles that allowed their corresponding MYCN-amplified (MA) clones to expand in the simulations. The genes are MYCN (M), the genes encoding the MAPK/RAS signalling pathway (MR1 and MR0), p53, p73, and HIF. MR1 denotes enhanced MAPK/RAS signalling in a MYCN-amplified neuroblastoma cell agent. MR0 denotes enhanced MAPK/RAS signalling in a neuroblastoma cell agent whose MYCN is not amplified. (B) Each bar quantifies the amount of variance in these gene expression profiles that can be explained by a particular principal component. (C) The lollipop chart presents the gene expression profile that parameterised the simulation that matched what is known [20] most closely. In this simulation, the three mutated clones dominated the wild-type clone and in each clone, the subclones with mutations in p53 and the genes encoding the MAPK/RAS signalling pathway dominated their peers. Furthermore, the number of living neuroblastoma cells in each clone increased during the simulation: the clones expanded. (D) The four time series confirm that, in the simulation parameterised by the gene expression profile presented in (C), all four clones (wild-type or WT, green; MYCN-amplified or MA, magenta; TERT-rearranged or TR, red; and ATRX-inactivated or AI, blue) expanded.