Model for genetic alterations in the development of colorectal cancer. Based on genetic analysis, at least two pathways are characterized in detail, which lead to colon cancer development. One pathway (indicated with red arrows) initiates with mutations in the adenomatous polyposis (APC) gene and chromosomal instability (CIN) followed by mutations in K-ras, deleted in colorectal cancer (DCC) and p53 genes. The second pathway (indicated with blue arrows) is initiated by the mutations in the mismatch repair (MMR) genes and microsatellite instability (MSI) followed by mutations in hMSH3, hMSH6, TGFβIIR, IGFIIR, PTEN, BLM, Tcf-4, Bax and E2F4 genes. Other pathways are less characterized, but a high degree of overlapping is expected among them. At least, seven gene mutations are needed to develop a normal epithelial cell into carcinoma. However, a cluster of gene and chromosome aberrations such as p15, p16, Bub1, cyclin D1, tPa, CEA, Nm23, MMP, E-cadherin (CDH1), CD44, 7q, 14q, 22q and 8p are observed in carcinoma and metastatic tumors. ASEF, APC-stimulated guanine nucleotide exchange factor; DLG, Drosophila discs large; EB1, end-binding protein 1, KAP3A, kinesin superfamily-associated protein 3A; MCR, mutator cluster region; NES, nuclear export signal; NLS, nuclear localization signal; PP2-B56α, protein phosphates 2A B56α subunit. This figure is adapted from reference .