In contrast, over-expression of these three genes along with knockdown of RB1 and over-expression of dominant-negative p53 (PARCB genes; ACB genes plus p53 and RB1 inactivation) drives temporal evolution from adenocarcinoma to an NE tumor that histologically and transcriptionally matches primary NE tumors, such as SCLC [50,51]. Here, RB1 is linked to small cell lung carcinoma.