Microsatellite Instability - Clinical Significance

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.