A novel algorithm for the detection of microsatellite instability in endometrial cancer using next-generation sequencing data

Molecular-based assay of microsatellite instability (MSI) detection in endometrial cancer has always been a challenge, due to the low sensitivity of PCR-base method and lacking of unified standard for the loci by NGS-base method. In this study, five commonly used microsatellite loci in PCR methods were added to the NGS panel to obtain the sequenced data. To analyze this data, a new and reliable algorithm called MSIPeak was proposed. The result presentation of MSI obtain by MSIPeak based on the NGS data were presented in a peak form similar to PCR methods. This algorithm was validated in the synthetic DNA samples, and then performed on MSI detection of endometrial cancers and compared with the immunohistochemistry base mismatch repair (MMR) status. Results showed that MSIPeak has much higher sensitivity than MSI-PCR, and has higher repeatability and applicability than other MSI-NGS based methods like MSISensor2 and MANTIS. The combination of MSIPeak and NGS is expected to become a widely used MSI detection method in cancer in the future.