Clinical Significance
MSI is a key factor in several cancers including colorectal, endometrial, ovarian and gastric cancers. Colorectal cancer studies have demonstrated two mechanisms for MSI occurrence.
- The first is in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome, where an inherited mutation in a mismatch-repair gene causes a microsatellite repeat replication error to go unfixed. Most cases result in changes in the lengths of dinucleotide repeats of the nucleobases cytosine and adenine (sequence: CACACACACA...). The change in nucleotide repeats is an indicator of a faulty DNA repair system, which can ultimately lead to cancer.
- The second mechanism whereby MSI is a marker for colorectal cancer is an epigenetic change that silences an essential mismatch-repair gene.
In both cases, microsatellite insertions and deletions indicate inappropriate DNA repair, resulting in uncontrolled cell division and tumor growth.
Read more about this topic: Microsatellite Instability
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