Our results accord with loss-of-function studies using several nontyrosine kinase tumour suppressors (e.g., Rb [53], PTEN [54], p16 [55], and p21 [56]), each of which has been associated with loss of HSC self-renewal, and it has been postulated that tissue stem cells might use a self-renewal disadvantage as barrier to tumor transformation [57]. This evidence concerns the gene RB1 and neoplasm.