Hereditary colon cancer genes.

Abstract

Colorectal cancer develops as the result of the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic epithelium to colon adenocarcinoma. The fact that colon cancer develops over 10–15 years and progresses through parallel histologic and molecular changes has permitted the study of its molecular pathology in more detail than other cancer types. Consequently, the specific nature of many of these cancer-associated genetic alterations has been determined over the last 15 years. The subsequent effect of these alterations on the cell and molecular biology of the cancer cells in which they occur has also begun to be revealed over the last decade. From the analysis of the molecular genesis of colon cancer, three key themes concerning the molecular pathogenesis of cancer have been established. The first is that cancer emerges via a multistep progression at both the molecular and the morphologic levels (). The second is that loss of genomic stability is a key molecular and pathophysiologic step in cancer formation (). The third is that hereditary cancer syndromes frequently correspond to germline forms of key genetic defects whose somatic occurrences drive the emergence of sporadic colon cancers ().