Taken together our RNA-seq and ChIP-seq analysis on host and KSHV genes indicates that tumorigenic K-Pα(+)S KS cells are more adapted to withstand oncogenic KSHV lytic gene expression possibly by regulating PDGFR, PI3K-AKT, p53 and cell cycle pathways, but also by repressing innate immune response genes upon induction of the lytic replication program. The gene discussed is TP53; the disease is Kaposi's sarcoma.