Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Gallon, R; Mühlegger, B; Wenzel, SS; Sheth, H; Hayes, C; Aretz, S; Dahan, K; Foulkes, W; Kratz, CP; Ripperger, T; Azizi, AA; Feldman, HB; Chong, AL; Demirsoy, U; Florkin, B; Imschweiler, T; Januszkiewicz-Lewandowska, D; Lobitz, S; Nathrath, M; Pander, HJ; Perez-Alonso, V; Perne, C; Ragab, I; Rosenbaum, T; Rueda, D; Seidel, MG; Suerink, M; Taeubner, J; Zimmermann, SY; Zschocke, J; Borthwick, GM; Burn, J; Jackson, MS; Santibanez-Koref, M; Wimmer, K.
A sensitive and scalable microsatellite instability assay to diagnose constitutional mismatch repair deficiency by sequencing of peripheral blood leukocytes.
Hum Mutat. 2019;
PubMed FullText FullText_MUG


Autor/innen der Med Uni Graz:
Seidel Markus

Dimensions Citations:

Plum Analytics:
Constitutional mismatch repair deficiency (CMMRD) is caused by germline pathogenic variants in both alleles of a mismatch repair gene. Patients have an exceptionally high risk of numerous paediatric malignancies, and benefit from surveillance and adjusted treatment. The diversity of its manifestation, and ambiguous genotyping results, particularly from PMS2, can complicate diagnosis and preclude timely patient management. Assessment of low-level microsatellite instability (MSI) in non-neoplastic tissues can detect CMMRD, but current techniques are laborious or of limited sensitivity. Here, we present a simple, scalable CMMRD diagnostic assay. It uses sequencing and molecular barcodes to detect low frequency microsatellite variants in peripheral blood leukocytes, and classifies samples using variant frequencies. We tested 30 samples from 26 genetically-confirmed CMMRD patients, and samples from 94 controls and 40 Lynch syndrome patients. All samples were correctly classified, except one from a CMMRD patient recovering from aplasia. However, additional samples from this same patient tested positive for CMMRD. The assay also confirmed CMMRD in 6 suspected patients. The assay is suitable for both rapid CMMRD diagnosis within clinical decision windows, and scalable screening of at-risk populations. Its deployment will improve patient care, and better define the prevalence and phenotype of this likely under-reported cancer syndrome. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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