Comparison of flow-FISH and MM-qPCR telomere length assessment techniques for the screening of telomeropathies
Ferreira, M. S. V. (University Hospital Aachen (Alemanya))
Kirschner, M. (University Hospital Aachen (Alemanya))
Halfmeyer, I. (University Hospital Aachen (Alemanya))
Estrada Barreras, Natalia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Xicoy, Blanca (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Isfort, S. (University Hospital Aachen (Alemanya))
Vieri, M. (University Hospital Aachen (Alemanya))
Zamora, Lurdes (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Abels, A. (University Hospital Aachen (Alemanya))
Bouillon, A. S. (University Hospital Aachen (Alemanya))
Begemann, M. (Institute of Human Genetics. Medical Faculty. RWTH Aachen University)
Schemionek, M. (University Hospital Aachen (Alemanya))
Maurer, A. (University Hospital Aachen (Alemanya))
Koschmieder, Steffen (University Hospital Aachen (Alemanya))
Wilop, S. (University Hospital Aachen (Alemanya))
Panse, J. (University Hospital Aachen (Alemanya))
Brümmendorf, Tim H (University Hospital Aachen (Alemanya))
Beier, Fabian (University Hospital Aachen (Alemanya))
Universitat Autònoma de Barcelona

Data:	2020
Resum:	Assessment of telomere length (TL) in peripheral blood leukocytes is part of the diagnostic algorithm applied to patients with acquired bone marrow failure syndromes (BMFSs) and dyskeratosis congenita (DKC). Monochrome multiplex-quantitative polymerase chain reaction (MM-qPCR) and fluorescence in situ hybridization (flow-FISH) are methodologies available for TL screening. Dependent on TL expressed in relation to percentiles of healthy controls, further genetic testing for inherited mutations in telomere maintenance genes is recommended. However, the correct threshold to trigger this genetic workup is still under debate. Here, we prospectively compared MM-qPCR and flow-FISH regarding their capacity for accurate identification of DKC patients. All patients (n = 105) underwent genetic testing by next-generation sequencing and in 16 patients, mutations in DKC-relevant genes were identified. Whole leukocyte TL of patients measured by MM-qPCR was found to be moderately correlated with lymphocyte TL measured by flow-FISH (r² = 0. 34; P < 0. 0001). The sensitivity of both methods was high, but the specificity of MM-qPCR (29%) was significantly lower compared with flow-FISH (58%). These results suggest that MM-qPCR of peripheral blood cells is inferior to flow-FISH for clinical routine screening for suspected DKC in adult patients with BMFS due to lower specificity and a higher rate of false-positive results.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	MM-qPCR ; Dyskeratosis congenita ; Flow-FISH ; Telomere length ; Telomeropathy
Publicat a:	Annals of the New York Academy of Sciences, Vol. 1466 Núm. 1 (2020) , p. 93-103, ISSN 1749-6632

DOI: 10.1111/nyas.14248
PMID: 31647584

11 p, 1.5 MB

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