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Defective mismatch repair, microsatellite mutation bias, and variability in clinical cancer phenotypes Shah SN; Hile SE; Eckert KACancer Res 2010[Jan]; 70 (2): 431-5Microsatellite instability is associated with 10% to 15% of colorectal, endometrial, ovarian, and gastric cancers, and has long been used as a diagnostic tool for hereditary nonpolyposis colorectal carcinoma-related cancers. Tumor-specific length alterations within microsatellites are generally accepted to be a consequence of strand slippage events during DNA replication, which are uncorrected due to a defective postreplication mismatch repair (MMR) system. Mutations arising within microsatellites associated with critical target genes are believed to play a causative role in the evolution of MMR-defective tumors. In this review, we summarize current evidence of mutational biases within microsatellites arising as a consequence of intrinsic DNA sequence effects as well as variation in MMR efficiency. Microsatellite mutational biases are generally not considered during clinical testing; however, we suggest that such biases may be clinically significant as a factor contributing to phenotypic variation among microsatellite instability-positive tumors.|*DNA Mismatch Repair[MESH]|*Microsatellite Instability[MESH]|Animals[MESH]|Colorectal Neoplasms, Hereditary Nonpolyposis/genetics/pathology[MESH]|Humans[MESH]|Neoplasms/*genetics/pathology[MESH] |
