Figure 1

The human colorectal tumorigenesis model proposed by Vogelstein and colleagues [12, 13] describes sequential inactivation of tumor suppressors ( APC, SMAD4 , and P53 ), activation of oncogene KRAS , and development of genomic instability. However, genes that are near the bona fide tumor suppressors and are disrupted in the human CRC appear not to be cancer-drivers, based on mouse model studies (DCC) or due to lack of evidence for the contribution to cancer (MCC).