The presence of these signaling events in both of these networks implies that transcriptional activity of p53 and its target genes might be affected by mutations in TSHZ3 and SETD2. Supporting this observation, SETD2 was shown to contribute to the regulation of p53 signaling by enhancing its transcriptional activities51 and in a recent study, TSHZ3 was identified as an inhibitor of p53 activity in lung cancer cell lines52. Here, SETD2 is linked to lung cancer.