Miniatura

Fitxers

707458.pdf (1.03 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2020-07-16

Llicència de publicació

cc-by-nc (c) González Acosta et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177396

High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1136/jmedgenet-2019-106272

Resum

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.

Matèries

Càncer colorectal, Reparació de l'ADN

Matèries (anglès)

Colorectal cancer, DNA repair

Citació

Col·leccions

Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

GONZÁLEZ ACOSTA, María isabel, MARÍN, Fátima, PULIAFITO, Benjamin, BONIFACI CANO, Núria, FERNÁNDEZ, Anna, NAVARRO, Matilde, SALVADOR, Héctor, 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. High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers. _Journal of Medical Genetics_. 2020. Vol. 57, núm. 4, pàgs. 269-273. [consulta: 25 de gener de 2026]. ISSN: 0022-2593. [Disponible a: https://hdl.handle.net/2445/177396]

Exportar metadades

JSON - METS

Compartir registre