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Detecting Microsatellite Instability in Endometrial, Colon, and Stomach Cancers Using Targeted NGS.

Ulyana Boyarskikh1, Andrey Kechin1, Evgeniy Khrapov1

  • 1Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.

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|October 28, 2023
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Summary

A new targeted next-generation sequencing (NGS) method accurately determines microsatellite instability (MSI) status in endometrial, colon, and stomach cancers. This MSI score can quantify the degree of instability, aiding in cancer diagnosis and treatment strategies.

Keywords:
endometrial cancersmicrosatellite instabilitytargeted NGS

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Microsatellite instability (MSI) is a key biomarker in several cancers.
  • Accurate MSI detection is crucial for diagnosis and treatment selection.

Purpose of the Study:

  • To develop and validate a targeted next-generation sequencing (NGS) method for MSI testing.
  • To establish an MSI score for quantifying instability in various cancer types.

Main Methods:

  • Selected 81 highly variable microsatellite loci for MSI analysis.
  • Developed an MSI scoring method and defined MSI status in endometrial, colon, and stomach cancers.
  • Validated the MSI score against MMR immunohistochemistry in 505 tumor samples.

Main Results:

  • The MSI score achieved high accuracy (AUC 0.99, sensitivity 92%, specificity 98%) across all tested cancer types.
  • MSI scores were significantly higher in colon and stomach cancers compared to endometrial cancer.
  • Optimizing loci for endometrial cancer improved accuracy to 100%.

Conclusions:

  • The developed MSI score accurately determines MSI status in endometrial, colon, and stomach cancers.
  • The MSI score provides a reliable method for quantifying the degree of microsatellite instability.
  • This targeted NGS approach offers a robust tool for MSI assessment in clinical oncology.