Abstract
Most cancers are genetically unstable and the instability exists at two distinct levels. Microsatellite instability (MIN) is observed at the nucleotide level, resulting in base substitutions or deletions or insertions of a few nucleotides. Chromosomal instability (CIN) is observed at the chromosome level and results in losses and gains of whole chromosomes or large portions. MIN is a characteristic of most hereditary nonpolyposis colorectal cancers (HNPCC). Approximately 15% of sporadic gastric and colorectal cancers also display MIN. Gastrointestinal cancers with MIN accumulate slippage-induced frameshift mutations in target genes such as type II TGFβ receptor and Bax. These cancers also have frequent aberrant DNA hypermethylation of tumor suppressor genes, including DNA mismatch repair gene hMLH1. A frequent loss of imprinting (LOI) of the insulin like growth factor II gene has been reported in colorectal cancers with MIN. On the other hand, mechanisms underlying CIN are beginning to be characterized. A small fraction of colorectal cancers have been shown to have mutations of the mitotic-checkpoint gene hBUB1 or hBUBR1. Cancers with MIN and those with CIN have been shown to exhibit fundamental differences in clinical, pathological, and molecular characteristics. From biological and clinical points of view, it is important to characterize the genetic instability of given tumors.
