Author Affiliation: Department of Cellular Pathology, Armed Forces Institute of Pathology, Washington, DC.
When a new strand of DNA is synthesized during the process of replication,
errors that are not immediately corrected by the 3′ to 5′ exonuclease
activity of DNA polymerase are corrected by a DNA mismatch repair (MR) system.
Mutations in gene coding for proteins that participate in the MR system allow
persistence of replication errors that would otherwise be repaired. Some of
these errors take the form of a phenomenon called microsatellite
instability—insertions or deletions of simple repetitive elements
within microsatellite sequences that occur throughout the genome. Approximately
0.1% to 0.5% of the population carries a germline mutation in 1 of 6 MR genes, hMSH2, hMSH6, hMLH1, hPMS1, hPMS2,
or hTGFBR2 (and perhaps others), that results in
a substantial increase in the probability of developing cancer of the colon
and rectum, endometrium, kidney, and other sites.1
Up to 80% of people who harbor a mutation in 1 of the MR genes will develop
colorectal cancer (accounting for approximately 5000 new colorectal cancers
in the United States yearly)1; up to 60% of
women will develop endometrial cancer.2
O'Leary TJ. Molecular Diagnosis of Hereditary Nonpolyposis Colorectal Cancer. JAMA. 1999;282(3):281–282. doi:10.1001/jama.282.3.281
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