MEM: An Algorithm for the Reliable Detection of Microsatellite Instability (MSI) on a Small NGS Panel in Colorectal Cancer

Cancers

Guillaume Herbreteau¹  Marc Guillaume Denis¹  Sandrine Théoleyre¹  Elise Pierre-Noël¹  Audrey Vallée¹  Simon Garinet²  Hélène Blons²  Stéphane Bézieau³  Fabrice Airaud³ 

[1] Laboratoire de Biochimie et Plateforme de Génétique Moléculaire des Cancers, CHU Nantes (Nantes University Hospital), 44093 Nantes, France;Plateforme de Génétique Moléculaire des Cancers, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris (Greater Paris University Hospitals), 75015 Paris, France;Service de Génétique Médicale, CHU Nantes (Nantes University Hospital), 44093 Nantes, France;

关键词: microsatellite instability;    deficient mismatch repair system;    colorectal cancer;    NGS;    expectation-maximisation algorithm;   

DOI  :  10.3390/cancers13164203

来源: DOAJ

【 摘 要 】

Purpose: MEM is an NGS algorithm that uses Expectation-Maximisation to detect the presence of unstable alleles from the NGS sequences of five microsatellites (BAT-25, BAT-26, NR-21, NR-24 and NR-27). The purpose of this study was to compare the MEM algorithm with a reference PCR method (MSI-PCR) and MisMatch Repair protein immunohistochemistry (MMR-IHC). Methods: FFPE colorectal cancer samples from 146 patients were analysed in parallel by MSI-PCR and NGS using the MEM algorithm. MMR-IHC results were available for 133 samples. Serial dilutions of an MSI positive control were performed to estimate the limit of detection. Results: the MEM algorithm was able to detect unstable alleles of each microsatellite with up to a 5% allelic fraction. Of the 146 samples, 28 (19.2%) were MSI in MSI-PCR. MEM algorithm results were in perfect agreement with those of MSI-PCR, at both MSI status and individual microsatellite level (Cohen’s kappa = 1). A high level of agreement was noted between MSI-PCR/MEM algorithm results and MMR-IHC results (Cohen’s kappa = 0.931). Conclusion: the MEM algorithm can determine the MSI status of colorectal cancer samples on a small NGS panel, using only five microsatellites approved by international guidelines, and can be combined with screening for targetable mutations.

【 授权许可】

Unknown