MSI is the condition of genetic hypermutability (predisposition to mutation) that results from impaired DNA mismatch repair (MMR). FDA approval of KEYTRUDA for MSI-high (MSI-H) solid tumors in May 2017, OPDIVO for MSI-H colorectal cancer in August 2017 and OPDIVO together with Ipilimumab for MSI-H colorectal cancer in July 2018 showed that MSI is a predictive biomarker for these anti-PD1 immunotherapies.
NovoPM™ 2.0-MSI Algorithm
- Using a training set of 35 paired tumor/normal samples with known MSI status (measured by Promega’s PCR-based MSI Analysis System, the current gold standard in clinical testing for MSI status), we applied three algorithms (MANTIS, msisensor and mSINGS) to analyze microsatellite status with NovoPM™ 2.0.
- The test covered a total of approximately 100 mononucleotide microsatellite loci and the significance of repeat length difference between tumor sample and the paired normal sample was used to determine the MSI status by each algorithm independently.
- The thresholds of MSI score were determined to be 0.4 for MANTIS, 0.2 for mSINGS, and 0.85 for msisensor.
- If the results from the three algorithms are concordant, the sample is considered MSS or MSI-H. If not, we recommend that the MSI status be verified with a PCR-based test.
The results of training set of 35 paired tumor/normal samples analyzed with NovoPM™ 2.0 are shown in Figure 1 (all the samples were with known MSI status measured by Promega’s PCR-based MSI Analysis System, the current gold standard in clinical testing for MSI status). The thresholds of MSI score were determined to be 0.4 for MANTIS, 0.2 for mSINGS, and 0.85 for msisensor.
Figure 1. NovoPM™ 2.0‒MSI scores of training set with 35 colorectal cancer FFPE samples including 6 MSI and 29 MSS. X-axis shows the sample ID and Y-axis shows the MSI score.