CD28 and cancer: For those tumors having a TP53/FBXW7 double–mutated genotype, the most significantly enriched cancer–related signaling pathways based on a NES > |1.75| and nominal p <  0.05 were the upregulation of glycolysis and metabolism of folate and pterines, overexpression of TP53 activity–related signaling, defective intrinsic pathway of apoptosis, interleukin 12 family signaling, CD28–dependent PI3K/AKT activity, homologous recombination, and alteration of the Fanconi anemia pathway (Figure 3E,F).