[Accumulation of genetic alterations during human tumor progression]

This study was designed to identify tumor suppressor genes whose inactivation is associated with the acquisition of metastatic ability in colorectal carcinoma. The results indicate that a specific subset of tumor suppressor genes is involved in metastasis of colorectal carcinoma. First, both the p53 and DCC genes were altered in 100% of liver metastases. Second, the incidence of loss of heterozygosity (LOH) at loci on chromosomes 13q, 14q, and 18q in liver metastases was higher than in primary tumors. Third, LOH or rearrangement not detected in the primary tumors was observed on chromosomes 13q, 14q and 18q in liver metastases from the same patients, while alterations on chromosome 17p were always detected in both lesions. These observations indicate that concordant inactivation of the p53 and DCC genes and inactivation of several tumor-suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential in colorectal carcinoma.