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Microsatellite instability (MSI) is a condition that signifies genetic hypermutability, often seen in various types of cancer. MSI is primarily linked to defects in DNA mismatch repair mechanisms, resulting in the accumulation of short repetitive DNA sequences. The presence of MSI is a crucial biomarker in the management of certain cancers, including colorectal, endometrial, and gastric cancers. It not only has diagnostic value but also informs treatment decisions, as tumors with high MSI are generally more responsive to immunotherapies. Identifying MSI status is thus vital for tailoring therapy and predicting patient outcomes.