Microsatellite Instability in Gastrointestinal Tract Cancers: A Brief Update
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- Oda, S., Zhao, Y. & Maehara, Y. Surg Today (2005) 35: 1005. doi:10.1007/s00595-005-3125-1
Microsatellite instability (MSI) was initially reported in colorectal cancer and, particularly, in hereditary nonpolyposis colorectal cancer (HNPCC). Since mutations in the genes functioning in DNA mismatch repair (MMR) were found in HNPCC kindred, this phenotype has been connected to a deficiency in MMR. The MSI+ phenotype is associated with various human malignancies. As MSI+ tumors appear to form a unique clinicopathological and molecular entity that is clearly distinct from that of classical colorectal tumors, which are accompanied by chromosomal instability (CIN), an exclusive pathway of tumorigenesis has been proposed in colorectal cancer. However, this scheme, comprising two mutually exclusive pathways, is now being reexamined, in light of a series of evidence accumulating in the literature, which relates to (a) distinction between high-level MSI (MSI-H) and low-level MSI (MSI-L), (b) heterogeneity in MSI-H, particularly in the sporadic and hereditary settings, (c) molecular mechanisms underlying the MSI+ phenotypes, and (d) relationships between the MSI+ and CIN phenotypes. Several molecular mechanisms may underlie repeat instability in eukaryotic cells. The relationship between MSI and defective MMR may be more complicated than has been suspected. The role of MMR deficiency in tumorigenesis in the digestive tract appears to be diverse and is not simple, even in the colorectum.
Key wordsReplication error (RER) DNA mismatch repair hMSH2 hMLH1
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