What is MSI-H/dMMR?
Microsatellite instability high/deficient mismatch repair (MSI-H/dMMR) are indicators of genomic instability:
MSI: Represents a change in the number of nucleotide repeats in DNA sequences, resulting in a different number of repeats than when the DNA was inherited.2
MSI-H: The presence of at least two unstable markers among five microsatellite markers analyzed (or ≥30% of the markers if a larger panel is used).2
dMMR: Represents a loss of function of the mismatch repair (MMR) pathway, a DNA repair pathway that plays a key role in maintaining genomic stability. dMMR is indicated by the loss of expression of one or more of the MLH1, MSH2, MSH6, and PMS2 proteins.2,3
How is MSI-H/dMMR measured? MSI-H is measured by polymerase chain reaction (PCR), and dMMR is detected by immunohistochemistry (IHC) for loss of expression of MMR proteins.3
Why is MSI-H/dMMR important? In MSI-H/dMMR patients with an increased number of mutations in a tumor, more neoantigens may be produced. Research is ongoing to determine how neoantigens are associated with increased T cell activation and how immune cell infiltration of tumors may be associated with response to therapy.