Genetic Instability and the Mutator Phenotype: Studies in Ulcerative Colitis

摘要: Tumorigenesis can be viewed as a process of cellular evolution in which individual preneoplastic or tumor cells acquire mutations that increase proliferative capacity and thus confer selective advantage. This evolutionary permits to escape the restrictions limit growth normal cells, such restraints imposed by immune system adverse metabolic conditions. The iterative selections underlying may dependent on ability mutate. Normal possess multiple mechanisms prevent from occurring at both nucleotide sequence level chromosome level. These include enzymes repair damaged DNA signal transduction pathways (checkpoints) induce cell cycle arrest apoptosis when stages are not appropriately completed. Normal prevented undergoing replication until damage is repaired, mitosis chromosomes properly attached mitotic spindles. 1,2 In contrast cancer characterized and, surprisingly, increasingly being found harbor genes control genomic stability. fact, ensure faithful transmission genetic information one generation next could early, critical events formation. 3 their paper this issue American Journal Pathology, Willenbucher et al document two forms instability, namely microsatellite instability chromosomal aberrations, occur during tumorigenesis associated with ulcerative colitis. 4 Importantly, these authors observed histologically nondysplatic tissue. Although findings cannot prove causality, they consistent view intrinsic required for