Marignani used a Cre-dependent Cas9 to generate mice models bearing KRasG12D and knocked out Lkb1 and p53 and showed that the simultaneous removal of these tumor suppressors activated mTOR, a marker of tumorigenesis and a pro-survival pathway, and increased the acetylation and methylation of histones 3 (H3) and H4, indicating a poor prognosis.91 This evidence concerns the gene TP53 and neoplasm.