Microsatellite Instability High/Deficient Mismatch Repair (MSI-H/dMMR)¹

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.

References
1. Yuan J et al. J Immunother Cancer. 2016; 4:3.
2. Hause RJ et al. Nat Med. 2016; 22:1342-1350.
3. Richman S. Int J Oncol. 2015; 47: 1189-1202.
4. Bogaert J, Prenen H. Ann Gastroenteral. 2014; 27:9-14
5. Schumacher TN, Schreiber RD. Science. 2015; 348 (6230): 69-74.
6. Overman MJ et al. Lancet Oncol. 2017. Doi. 10.1016/S1470-2045(17) 30422-9.
7. Le DT et al. Oral presentation at ASCO 2016.
8. Hochster HS et al. Poster presentation at ASCO GI 2017. Abstract 673.