The proposed model states that the RER+ carcinogenesis is divided into two clearly distinct evolutive phases: (1) a preliminary phase starting with the counter-selective loss of mismatch repair function, in which most clones with the RER mutator phenotype are eliminated through apoptosis or an accelerated aging process; (2) an explosive phase that is initiated only if mutations blocking apoptosis and senescence, rapidly acquired during the short life span of the nontransformed RER+ clones, eventually rescue one RER+ cell that gives rise to the malignant clone.
C0596263
Carcinogenesis