Management of colorectal cancer (CRC) patients relies on the accurate determination of microsatellite instability (MSI) status. MSI status can have an influence on therapy decisions centered on immune checkpoint inhibitors. In this study a novel droplet digital PCR (ddPCR) kit for MSI status determination was validated across 2 separate CRC patient cohorts: 102 tumor samples from the ALGECOLS cohort and 129 plasma samples from the RASANC cohort. Each cohort was assessed for MSI status using the novel ddPCR kit and compared to historical and/or newly obtained results, (either immunohistochemistry analysis or PCR amplification). Concordance between ddPCR and conventional MSI determination methods for the analysis of tissue samples was 97.1% for ALGECOLS. When looking at positive ctDNA samples, a strong concordance was observed for the RASANC cohort. This study illustrates that ddPCR MSI testing represents a rapid, sensitive and accurate method with a strong correlation to established methods. Moreover, the ability of the described approach to monitor MSI status in both tumor and plasma enhances the potential for the use of MSI status in longitudinal monitoring of CRC patients.

The authors declare a potential conflict of interest and state it below MH, AC, JL, JY are employees of Bio-Rad Laboratories

This work was supported by the APHP (grant no. CRC06043), the Poitiers University Hospital, the INSERM-DGOS, the Ministere Enseignement Superieur et de la Recherche, the University Paris City, the CNRS, the INSERM, the Centre de Recherche des Cordeliers and the ligue nationale contre le cancer (no. EL2016.LNCC). JL, JY, AC and MH are Bio-Rad employees.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Cohort 1: Ninety-six (96) FF and 6 FFPE CRC samples with known MSI status were retrospectively selected from the ALGECOLS cohort (according to availability of samples) approved by the Ile-de-France ethics committee number 2 (NCT01198743). Cohort 2: From the RASANC protocol, approved by the Ile-de-France IV ethics committee, 129 cell-free DNA (cfDNA) samples were analyzed (according to availability)

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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All data produced in the present study are available upon reasonable request to the authors