An innovative and accurate next-generation sequencing-based microsatellite instability detection method for colorectal and endometrial tumors.

The detection of microsatellite instability (MSI) and mismatch repair deficiency (dMMR) has become mandatory for most tumors in recent years, owing to the development of immune checkpoint inhibitors (ICIs) as a highly effective therapy for dMMR/MSI tumors. The timely and efficient detection of MSI is valuable, and new methods are increasingly being developed. To date, MMR assessment has been performed using immunohistochemistry (MSI IHC) of the four MMR proteins and/or MSS/MSI using polymerase chain reaction (MSI-PCR), mostly using the pentaplex panel. The implementation of next-generation sequencing (NGS) for MSI (MSI-NGS) analysis would improve the effectiveness at a lower cost and in less time. This study describes the development of 8 new microsatellites combined with a classification algorithm, termed "Octaplex CaBio-MSID" (for Cancérologie Biologique MSI Detection tool), to assess MSI using NGS. A series of 303 CRC and 88 EC samples were assessed via MSI-NGS using the Octaplex CaBio-MSID. The sensitivity and specificity of Octaplex CaBio-MSID were 98.4% and 98.4% for CRCs, and 89.3% and 100% for ECs, respectively. This new NGS-based MSI detection method outperforms previously published methods (i.e. IdyllaTM , OncoMateTM MSI Dx, and Foundation One® CDx). Although highly efficient, Octaplex CaBio-MSID requires validation in a larger independent series of different tumor types.