MSI-WES: a simple approach for microsatellite instability testing using whole exome sequencing

Future Oncol. 2021 Sep;17(27):3595-3606. doi: 10.2217/fon-2021-0132. Epub 2021 Jul 22.

Abstract

Aim: To demonstrate that MSI-WES is an accurate testing method for microsatellite instability (MSI). Materials & methods: Microsatellite-based indels were counted in the variant call-formatted whole exome sequencing (WES) data of 441 gastric cancer cases using Unix-based algorithms, and the counts expressed as a fraction of the genome sequenced to obtain next-generation sequencing-based MSI indices. Results: The next-generation sequencing-based MSI indices showed a near-perfect concordance with PCR-based MSI status, and moderate to good correlations with the molecular targets of MSI index, MLH1 expression and MLH1 methylation status, at a level comparable to the strengths of correlation between PCR-based MSI status and molecular targets of MSI index/MLH1 expression and methylation. Conclusion: MSI-WES is a valid, adequate and sensitive approach for testing MSI in cancer.

Keywords: MLH1 methylation and expression; MSI indices; PCR; gastric cancer; indels; microsatellite instability; molecular targets of MSI; next-generation sequencing; variant call format files; whole exome sequencing.

MeSH terms

  • Exome Sequencing*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Microsatellite Instability*
  • Polymerase Chain Reaction
  • Stomach Neoplasms / genetics*