MAY 08, 2020 8:00 AM PDT

Development of a novel molecular MSI assay with an expanded panel and automated MSI status calling


Event Date & Time
DATE:  May 8, 2020
TIME:   8:00am PT, 11:00am ET
Microsatellite instability (MSI) is the condition of genetic hypermutability that results from impaired DNA mismatch repair (MMR). Studies indicate that the presence of high levels of MSI (MSI-H) might be predictive of Lynch syndrome, a hereditary condition associated with increased cancer risk across a variety of tumor types, including colorectal, gastric, and endometrial cancers—and MSI-H tumors are known to be more sensitive to immune checkpoint inhibitor treatments than microsatellite stable (MSS) tumors.
Clinical researchers have indicated that MSI detection techniques are few and have limitations. For example, 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. To improve upon current MSI analysis methods, Thermo Fisher Scientific developed the Applied Biosystems™ TrueMark™ MSI Assay. This multiplex fluorescent PCR panel consists of 8 markers used historically in Lynch syndrome and MSI identification as well as 5 novel quasi-monomorphic homopolymers. Two human identification STRs are included for sample traceability. This 15-plex fluorescent PCR fragment analysis assay is performed via a standard capillary electrophoresis workflow and requires low DNA input. The included software automatically detects unstable microsatellite markers and sample contamination or mix-up.
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 molecular MSI assay due to the expanded marker set. The combination of our expanded marker set and automated analysis software constitutes an important tool for studying MSI.
Learning Objectives:
  • Learn about the importance of MSI assessment in cancer research
  • Understand the difference between dMMR analysis and MSI analysis
  • Discover a new molecular assay for MSI research analysis
For research use only. Not for use in diagnostic procedures.
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