Genetic instability in colorectal cancer

See article on page553 The development of neoplasia has been thought to be associated with genetic alterations for many years. In colorectal cancer two specific types of genetic instability have been defined. One is associated with chromosomal instability and the other with DNA microsatellite instability, also known as replication errors.1 The mechanism underlying tumorigenesis leads to profound differences in the pathological features, prognosis and response to chemotherapy of these two types of colorectal cancer. The great majority of colorectal cancers are aneuploid with a variable chromosome complement. However, between 10 and 15% of colorectal cancers are near diploid and exhibit DNA microsatellite instability in which replication errors may be demonstrated within repetitive sequences of tumour DNA which are not present in the normal DNA of the individual. Tumours with microsatellite instability occur more frequently in younger patients, are more frequently proximal to the splenic flexure and exhibit exophytic growth, poor differentiation, extracellular mucin production, and a Crohn’s-like …