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Title: High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers
Author: González Acosta, María Isabel
Marín, Fátima
Puliafito, Benjamin
Bonifaci Cano, Núria
Fernández, Anna
Navarro, Matilde
Salvador, Hector
Balaguer Prunés, Francesc
Iglesias, Silvia
Velasco, Àngela
Grau Garcés, Èlia
Moreno Aguado, Víctor
González Granado, Luis Ignacio
Guerra García, Pilar
Ayala, Rosa
Florkin, Benoît
Kratz, Christian
Ripperger, Tim
Rosenbaum, Thorsten
Januszkiewicz-Lewandowska, Danuta
Azizi, Amedeo A.
Ragab, Iman
Nathrath, Michaela
Pander, Hans-Jürgen
Lobitz, Stephan
Suerink, Manon
Dahan, Karin
Imschweiler, thomas
Demirsoy, Ugur
Brunet, Joan
Lázaro García, Conxi
Rueda, Daniel
Wimmer, Katharina
Capellá, G. (Gabriel)
Pineda, Marta
Keywords: Càncer colorectal
Reparació de l'ADN
Colorectal cancer
DNA repair
Issue Date: 16-Jul-2020
Publisher: BMJ Publishing Group
Abstract: Introduction: Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are hereditary cancer syndromes associated with mismatch repair (MMR) deficiency. Tumours show microsatellite instability (MSI), also reported at low levels in non-neoplastic tissues. Our aim was to evaluate the performance of high-sensitivity MSI (hs-MSI) assessment for the identification of LS and CMMRD in non-neoplastic tissues. Materials and methods: Blood DNA samples from 131 individuals were grouped into three cohorts: baseline (22 controls), training (11 CMMRD, 48 LS and 15 controls) and validation (18 CMMRD and 18 controls). Custom next generation sequencing panel and bioinformatics pipeline were used to detect insertions and deletions in microsatellite markers. An hs-MSI score was calculated representing the percentage of unstable markers. Results: The hs-MSI score was significantly higher in CMMRD blood samples when compared with controls in the training cohort (p<0.001). This finding was confirmed in the validation set, reaching 100% specificity and sensitivity. Higher hs-MSI scores were detected in biallelic MSH2 carriers (n=5) compared with MSH6 carriers (n=15). The hs-MSI analysis did not detect a difference between LS and control blood samples (p=0.564). Conclusions: The hs-MSI approach is a valuable tool for CMMRD diagnosis, especially in suspected patients harbouring MMR variants of unknown significance or non-detected biallelic germline mutations. Keywords: constitutional mismatch repair deficiency; highly sensitive methodologies; lynch syndrome; microsatellite instability; next generation sequencing.
Note: Reproducció del document publicat a:
It is part of: Journal of Medical Genetics, 2020, vol. 57, num. 4, p. 269-273
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ISSN: 0022-2593
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Ciències Clíniques)

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