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Critical Reviews™ in Oncogenesis

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v13.i3.20
pages 229-257

Slip Slidin' Away: A Duodecen-nial Review of Targeted Genes in Mismatch Repair Deficient Colorectal Cancer

Ellen C. Royrvik
Department of Cancer Prevention, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center; Center for Cancer Biomedicine, University of Oslo, Norway
Terje Ahlquist
Department of Cancer Prevention, Institute for Cancer Research, Oslo University Hospital— Radiumhospitalet, Oslo, Norway
Torbjorn Rognes
Center for Molecular Biology and Neuroscience, Rikshospitalet-Radiumhospital et Medical Center; Department of Informatics, University of Oslo, Norway
Ragnhild A. Lothe
Department of Cancer Prevention, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center; Center for Cancer Biomedicine, University of Oslo; Department of Molecular Biosciences, University of Oslo, Norway

ABSTRACT

Roughly 15% of colorectal tumors are characterized by microsatellite instability (MSI), a deficiency caused by defective DNA mismatch repair, which leads to profuse insertions and deletions in microsatellites. Downstream target genes of this defective repair are those prone to exhibit these insertion/deletion mutations in their coding regions and potentially having functional consequences in, and providing a growth advantage for, the cancer cell. This review presents the last 12 years of research on these MSI target genes, systematizing the mutation details of the more than 160 genes identified to date, and includes their mutation frequencies in colorectal and other MSI (e.g., gastric and endometrial) tumors. Functional aspects of certain targets and the target gene concept itself are also discussed, as is the comparative wealth of potential target genes— assessed by scanning the coding sequences of the human genome for mononucleotide repeats—yet to be investigated.