Defective mismatch repair, microsatellite mutation bias, and variability in clinical cancer phenotype

Cancer Res. 2010 Jan 15

Shah SN, Hile SE, Eckert KA.
Department of Pathology, Gittlen Cancer Research Foundation, Pennsylvania State University College of Medicine, Hershey, Pennsylvania

Microsatellite instability is associated with 10% to 15% of colorectal, endometrial, ovarian, and gastric cancers, and has long been used as a diagnostic tool for (Lynch Syndrome) 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.