The genetics of colorectal carcinoma

Colorectal neoplasms begin as monoclonal cell populations, presumably arising from a single mutation or from a series of mutations in a single epithelial cell. Identification of the earliest mutation has been elusive. The resulting neoplastic clone is genetically unstable, perhaps owing to reduced methyl content of the deoxyribonucleic acid (DNA) molecules. Loss of DNA repair mechanisms may also be a factor. There are multiple genetic pathways to colorectal carcinoma (CRC). The multiplicity of mutations which are often associated with carcinogenesis suggests that the cancer cell is specifically adapted to its parasitic role. This is especially apparent when cancer cells become capable of invasion and metastasis. Early therapeutic experiments in vitro suggest that the carcinogenic process may be disrupted by correction of any one of the multiple genetic defects.