ABSTRACT
Cancer development requires multiple oncogenic mutations (Table 1). These mutations confer phenotypic characteristics essential for malignancy, such as limitless replicative potential, avoidance of cell death, self-suffi ciency with respect to growth-stimulatory signals, insensitivity to growth inhibitory signals, induction of angiogenesis, tissue invasiveness, and metastatic potential (Hanahan and Weinberg 2000). Malignant transformation of fi broblasts may be accomplished by transfection leading to 8 genetic changes, one in each of 4 dominant oncogenes, and 2 each in 2 recessive oncogenes (Rangarajan et al. 2004). Moreover, epidemiologic studies are consistent with 2-12 rate limiting steps for oncogenesis, depending on the tumor type, and at least some of these are likely to be genetic changes (Beckman and Loeb 2005b).
