Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones

Resistance mutations can be detected in 75% of CLL patients progressing under BTK inhibitor therapy. Using semiquantitative wild-type-blocking (WTB) RT-PCR for BTK and Sanger sequencing for PLCG2 mutations, we compared detection sensitivity of cellular versus circulating tumor DNA (ctDNA) in 20 samp...

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Autores principales: Trummer, Arne, Schier, Wiebke, Krauter, Jürgen, Hannig, Horst, Christmann, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706612/
https://www.ncbi.nlm.nih.gov/pubmed/36457814
http://dx.doi.org/10.1016/j.lrr.2022.100359
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author Trummer, Arne
Schier, Wiebke
Krauter, Jürgen
Hannig, Horst
Christmann, Jens
author_facet Trummer, Arne
Schier, Wiebke
Krauter, Jürgen
Hannig, Horst
Christmann, Jens
author_sort Trummer, Arne
collection PubMed
description Resistance mutations can be detected in 75% of CLL patients progressing under BTK inhibitor therapy. Using semiquantitative wild-type-blocking (WTB) RT-PCR for BTK and Sanger sequencing for PLCG2 mutations, we compared detection sensitivity of cellular versus circulating tumor DNA (ctDNA) in 20 sample pairs of 13 consecutive patients. With an assay sensitivity of 0.06%, 7 patients had a BTK-C481S and one a PLCG2-G667E mutation. Cellular DNA was positive in 10 but ctDNA only in 6 samples, giving false-negative results in samples with low mutational burden. In summary, WTB-PCR is cost-effective and routinely applicable but misses low frequency mutations when using ctDNA.
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spelling pubmed-97066122022-11-30 Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones Trummer, Arne Schier, Wiebke Krauter, Jürgen Hannig, Horst Christmann, Jens Leuk Res Rep Article Resistance mutations can be detected in 75% of CLL patients progressing under BTK inhibitor therapy. Using semiquantitative wild-type-blocking (WTB) RT-PCR for BTK and Sanger sequencing for PLCG2 mutations, we compared detection sensitivity of cellular versus circulating tumor DNA (ctDNA) in 20 sample pairs of 13 consecutive patients. With an assay sensitivity of 0.06%, 7 patients had a BTK-C481S and one a PLCG2-G667E mutation. Cellular DNA was positive in 10 but ctDNA only in 6 samples, giving false-negative results in samples with low mutational burden. In summary, WTB-PCR is cost-effective and routinely applicable but misses low frequency mutations when using ctDNA. Elsevier 2022-11-09 /pmc/articles/PMC9706612/ /pubmed/36457814 http://dx.doi.org/10.1016/j.lrr.2022.100359 Text en © 2022 Published by Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Trummer, Arne
Schier, Wiebke
Krauter, Jürgen
Hannig, Horst
Christmann, Jens
Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones
title Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones
title_full Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones
title_fullStr Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones
title_full_unstemmed Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones
title_short Circulating versus cellular tumor DNA for the detection of BTK resistant CLL clones
title_sort circulating versus cellular tumor dna for the detection of btk resistant cll clones
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9706612/
https://www.ncbi.nlm.nih.gov/pubmed/36457814
http://dx.doi.org/10.1016/j.lrr.2022.100359
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