Interestingly, pathways including PI3K-Akt signaling, Rap1 signaling, axon guidance, microRNA in cancer, focal adhesion, and ECM-receptor interaction were upregulated and their gene promoters were hypo-methylated during tumorigenesis with the virus, and these same pathways were down-regulated and gene promoters were hyper-methylated during tumor formation following loss of the virus (Fig 4N and 4O). The gene discussed is AKT1; the disease is cancer.