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Microsatellite Instability (MSI) Analysis for Biomarker Discovery

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Creative Biolabs has organized outstanding scientists who have developed a powerful Immune Monitoring Platform for Immune Biomarker Development for many years. A high level of microsatellite instability (MSI) is an emerging predictive and prognostic biomarker for immunotherapy response in cancer. Creative Biolabs is pleased to share our cutting-edge technology and extensive expertise in MSI analysis to facilitate our clients' research in MSI biomarker development.

Methods for the Detection of MSI Biomarker

Microsatellite sequences are 1-6 bp short tandem repeats, which are highly mutable and ubiquitous in eukaryotic genomes. MSI usually arises from germline mutations in components of the mismatch repair (MMR) machinery. MSI-high has been recognized as a biomarker for immune checkpoint inhibitor therapy in cancers. At present, MSI status is most commonly determined using PCR-based MSI testing and immunohistochemistry (IHC) based MSI testing. PCR-based MSI testing analyzes five to seven highly conserved microsatellite markers while IHC-based MSI testing involves staining for the MMR proteins. However, an isolated loss of MMR protein expression may not lead to elevated microsatellite alterations and conversely, positive staining may result from retained antigenicity of non-functional MMR proteins. Accordingly, PCR-based MSI testing and IHC-based MSI testing only correlate in about 90% of cases. Over the last decade, thanks to the advent of deep sequencing technology, several next-generation sequencing (NGS)-based algorithms have been developed to characterize MSI. Mutations with unknown clinical significance but low levels could be efficiently detected.

Microsatellite Instability (MSI) Analysis for Biomarker Discovery

MSI Analysis for Biomarker Discovery at Creative Biolabs

Creative Biolabs combines a diverse range of Technologies with a team of seasoned scientists who are experts in the MSI analysis for biomarker discovery. Our scientists have developed several efficient strategies for MSI analysis, including IHC-based MSI testing, PCR-based MSI testing and NGS-based MSI testing. We are dedicated to serving every unique need of our clients in biomarker discovery projects.

Microsatellite Instability (MSI) Analysis for Biomarker Discovery 2

  • IHC-based MSI testing
  • IHC of mismatch repair (MMR) proteins are used to determine whether tumors are MSI-positive. High accuracy between IHC of MMR proteins and MSI has been reported. Immunostaining of MMR proteins is simple and can be easily performed. IHC involves staining for the MMR proteins (MLH1, MSH2, MSH6, and PMS2).

  • PCR-based MSI testing
  • DNA from tumor samples can be tested for microsatellite instability using a panel consisting of mono- and di-nucleotide markers. PCR-based MSI testing can be conducted in combination with MMR IHC. In this assay, other markers are needed, such as MONO-27, BAT-40, NR-21, NR-24.

  • NGS-based MSI testing
  • NGS-based MSI testing enables massively parallel sequencing of MMR genes. NGS technology enables more in-depth sequencing. Mutations with unknown clinical significance but low levels could be identified.

Equipped with a team of seasoned scientists with facilities and processes designed specifically to meet very challenging requirements in MSI analysis for biomarker discovery, Creative Biolab offers fast, reliable support d for any phase of biomarker development projects for immune monitoring. For more detailed information, please feel free to contact us or directly send us an inquiry.

Reference

  1. Bonneville, R.; et al. Detection of microsatellite instability biomarkers via next-generation sequencing. InBiomarkers for Immunotherapy of Cancer. 2020, 119-132.
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