Gonzalez-Acosta, Maribel ORCID: 0000-0002-2468-3876, Marin, Fatima ORCID: 0000-0003-3534-0091, Puliafito, Benjamin, Bonifaci, Nuria, Fernandez, Anna, Navarro, Matilde, Salvador, Hector ORCID: 0000-0002-2515-0019, Balaguer, Francesc, Iglesias, Silvia, Velasco, Angela, Garces, Elia Grau, Moreno, Victor ORCID: 0000-0002-2818-5487, Gonzalez-Granado, Luis Ignacio ORCID: 0000-0001-6917-8980, Guerra-Garcia, Pilar ORCID: 0000-0002-7740-0614, Ayala, Rosa, Florkin, Benoit, Kratz, Christian, Ripperger, Tim, Rosenbaum, Thorsten, Januszkiewicz-Lewandowska, Danuta, Azizi, Amedeo A., Ragab, Iman, Nathrath, Michaela, Pander, Hans-Juergen, Lobitz, Stephan, Suerink, Manon, Dahan, Karin, Imschweiler, Thomas, Demirsoy, Ugur, Brunet, Joan ORCID: 0000-0003-1945-3512, Lazaro, Conxi, Rueda, Daniel ORCID: 0000-0002-5377-8890, Wimmer, Katharina, Capella, Gabriel and Pineda, Marta (2020). High-sensitivity microsatellite instability assessment for the detection of mismatch repair defects in normal tissue of biallelic germline mismatch repair mutation carriers. J. Med. Genet., 57 (4). S. 269 - 274. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-6244

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gonzalez-Acosta, MaribelUNSPECIFIEDorcid.org/0000-0002-2468-3876UNSPECIFIED
Marin, FatimaUNSPECIFIEDorcid.org/0000-0003-3534-0091UNSPECIFIED
Puliafito, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonifaci, NuriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Navarro, MatildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salvador, HectorUNSPECIFIEDorcid.org/0000-0002-2515-0019UNSPECIFIED
Balaguer, FrancescUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iglesias, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velasco, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garces, Elia GrauUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moreno, VictorUNSPECIFIEDorcid.org/0000-0002-2818-5487UNSPECIFIED
Gonzalez-Granado, Luis IgnacioUNSPECIFIEDorcid.org/0000-0001-6917-8980UNSPECIFIED
Guerra-Garcia, PilarUNSPECIFIEDorcid.org/0000-0002-7740-0614UNSPECIFIED
Ayala, RosaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Florkin, BenoitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kratz, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ripperger, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenbaum, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Januszkiewicz-Lewandowska, DanutaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Azizi, Amedeo A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ragab, ImanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nathrath, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pander, Hans-JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lobitz, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suerink, ManonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahan, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imschweiler, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demirsoy, UgurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brunet, JoanUNSPECIFIEDorcid.org/0000-0003-1945-3512UNSPECIFIED
Lazaro, ConxiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rueda, DanielUNSPECIFIEDorcid.org/0000-0002-5377-8890UNSPECIFIED
Wimmer, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capella, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pineda, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-338657
DOI: 10.1136/jmedgenet-2019-106272
Journal or Publication Title: J. Med. Genet.
Volume: 57
Number: 4
Page Range: S. 269 - 274
Date: 2020
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-6244
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EUROPEAN CONSORTIUM CARE; LYNCH SYNDROME; GUIDELINES; DIAGNOSIS; ONSET; MLH1Multiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33865

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item