Microsatellite instability

Microsatellite instability (MSI) is a condition that appears in the DNA of specific cells (such as cancer cells) where the number of microsatellite repeats in these cells is different than the repeats in normal DNA. Microsatellites, also known as short tandem repeats (STRs), are repeating sequences of 1-6 base pairs of DNA. MSI is a form of genomic instability and is found in many types of human cancer.

Causes

MSI is caused by defects in the mismatch repair (MMR) system of the cell. The MMR system corrects errors that spontaneously occur during DNA replication, such as single base mismatches or short insertions and deletions. The proteins involved in MMR correct these errors by forming a complex that binds to the mismatched DNA, excises the error, and uses the original DNA strand as a template to correct the mismatch.

Role in Cancer

MSI is a common feature of certain types of cancer. It is most often associated with colorectal cancer, endometrial cancer, and gastric cancer. In these cancers, the MMR system is defective, leading to an accumulation of errors in the DNA and resulting in genomic instability. This instability can lead to the development of cancer.

Diagnosis

Diagnosis of MSI involves testing the DNA of tumor cells for the presence of microsatellite instability. This is typically done using polymerase chain reaction (PCR) to amplify microsatellite regions, followed by analysis of these regions to detect any changes in the number of repeats.

Treatment and Prognosis

The presence of MSI in a tumor can have implications for treatment and prognosis. Tumors with high levels of MSI (known as MSI-H) are often more responsive to immunotherapy than tumors without MSI. Additionally, patients with MSI-H tumors often have a better prognosis than those with microsatellite stable (MSS) tumors.

See Also

• DNA mismatch repair
• Genomic instability
• Colorectal cancer
• Endometrial cancer
• Gastric cancer