MICROSATELITE INSTABILITY

MSI is an effective marker for the diagnosis of Lynch syndrome and the prediction of prognosis in the treatment of certain types of cancer. MSI is also an approved biomarker for predicting the efficacy of anti-PD-L1 / PD-1 immunotherapeutic agents, including Keytruda and Opdivo in solid tumors.

Analysis of microsatellite instability (MSI)

Microsatellite instability (MSI) is the condition of genetic hypermutability (predisposition to mutation) that results from the repair of altered DNA mismatch (MMR) in tumors. MSI is an effective marker for the diagnosis of Lynch syndrome and the prediction of prognosis in the treatment of certain types of cancer. MSI is also an approved biomarker for predicting the efficacy of anti-PD-L1 / PD-1 immunotherapeutic agents, including Keytruda and Opdivo in solid tumors.

MSI Algorithm

 

Using a training set of matched tumor / normal samples with known MSI status (measured by PCR), we identified 19 of 43 mononucleotide microsatellite loci covered by DIPPRECISION whose repeated lengths can reliably reflect the MSI status of the tumor samples. These 19 loci are defined as the "set of MSI markers".

 

For each tumor sample to be analyzed, the histogram of reading counts for different repetition lengths of each locus in the set of MSI markers is compared to that of the normal paired sample using the Mann-Whitney U test. A locus is considered unstable if the P value is less than 0.05.

 

The percentage of unstable loci in the set of MSI markers is calculated as the NovoPM MSI score. The following thresholds are established with another set of training samples:

 

  • MSI score> 0.23: the tumor sample is MSI.

 

  • 0.23 ≥ MSI score ≥ 0.17: the MSI status of the tumor sample can not be determined with this method. The use of a conventional method (for example, PCR) is recommended.

 

  • MSI score <0.17: the tumor sample is MSS.

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