RB1 and pituitary tumor: Since no higher incidence of pituitary tumors was found upon combined Rb loss and Bmi1 over expression, this indicates that the oncogenic function of Bmi1 is dependent on the presence of a functional p16INK4A locus, this is substantiated by the observation that in the latter case, 40% of the tumors are positive in IHC for Bmi1, indicating that the remaining 60% of the tumors have inactivated the Rb allele independent of Bmi1 over expression.