JUL 02, 2020 12:15 PM SGT

Microsatellite instability analysis for studying immunotherapy and Lynch syndrome-related cancers

Speaker

Abstract

Microsatellite instability (MSI) is a hypermutation phenotype that results from impaired DNA mismatch repair (MMR). The presence of high levels of MSI (MSI-H) is potentially predictive of Lynch syndrome, a hereditary condition associated with increased cancer risk across a variety of tumor types, including colorectal, gastric, and endometrial cancers. Additionally, MSI-H tumors are known to be more sensitive to immune checkpoint inhibitor treatment than microsatellite stable (MSS) tumors.

Traditional MSI analysis methods have limitations. IHC staining for DNA MMR enzyme reactivity is semiquantitative at best and relies on subjective interpretation that varies from person to person, while commonly used molecular MSI assays have insufficient markers for applications across multiple tumor types and cumbersome data analysis. The new Applied Biosystems™ TrueMark™ MSI Assay helps overcome these limitations with an expanded 13-microsatellite marker panel for accurate MSI analysis of multiple cancer sample types beyond just colorectal cancer. This 15-plex fluorescent PCR fragment analysis assay is performed via a standard capillary electrophoresis workflow with low DNA input. The included software offers automated calling and does not require running tumor and matched normal tissue.

To demonstrate the utility of the TrueMark MSI Assay, we performed a retrospective study using FFPE research samples derived from colon, gastric, and endometrial cancers. The assay produced high concordance with IHC and fewer ambiguous results relative to an alternative, commercially available MSI assay due to the expanded marker set. The combination of our expanded panel and automated analysis software constitutes an important tool for studying MSI.


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