Fig. 1

Multistep pathway from normal cell to metastatic colon carcinoma. The rate-limiting step is postulated to be the loss of the APC gene on chromosome 5. Individuals with familial adenomatous polyposis (FAP) inherit the first mutation (APC gene) and only need to acquire a second mutation. Other individuals need to acquire both mutations in the same cell lineage. Additional genetic damage is accumulated, including loss of genes on 17p, exemplified p53, and 18q, as well as other changes. These can occur in any order and result in progressively abnormal cells, eventually capable of metastasis (Figure provided by Bert Vogelstein)