GENETIC INSTABILITY AND CHROMOSOMAL-ABERRATIONS IN COLORECTAL-CANCER - A REVIEW OF THE CURRENT MODELS

Our understanding of the pathogenesis of cancer has undergone a revolu tion over the past decade. Tumors develop by the accumulation of damag e to genes that regulate cell growth. Many of the genes responsible fo r disregulation of cell growth have been identified, as have the proce sses that lead to the genetic damage. One of the most important concep ts that has facilitated our understanding of carcinogenesis is that of genetic or ''genomic'' instability, which is required to permit a suf ficient amount of genetic damage to accumulate to permit the neoplasti c phenotype to emerge and evolve. Two mechanisms that lead to genomic instability-one of which involves the loss of chromosomal fragments fr om the nucleus, and a second which is characterized by microsatellite instability-are discussed.