Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma

High-throughput sequencing of cell-free DNA (cfDNA) has emerged as a promising noninvasive approach in lymphomas, being particularly useful when a biopsy specimen is not available for molecular analysis, as it frequently occurs in primary mediastinal large B-cell lymphoma (PMBL). We used cfDNA for g...

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Autores: Rivas-Delgado, Alfredo, Nadeu, Ferran, Andrade-Campos, Marcio, López, Cristina, Enjuanes¸ Anna, Mozas, Pablo, Frigola, Gerard, Colomo Saperas, Luis Alberto, Sánchez González, Blanca, Villamor, Neus, Beà, Sílvia, Campo, Elias, Salar, Antonio, Giné, Eva, López Guillermo, Armando, Bellosillo Paricio, Beatriz
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/55508
Acceso en línea:http://hdl.handle.net/10230/55508
http://dx.doi.org/10.3390/diagnostics12071575
Access Level:acceso abierto
Palabra clave:Cell-free DNA
Copy number analysis
Mutational profile
Primary mediastinal large B-cell lymphoma
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spelling Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphomaRivas-Delgado, AlfredoNadeu, FerranAndrade-Campos, MarcioLópez, CristinaEnjuanes¸ AnnaMozas, PabloFrigola, GerardColomo Saperas, Luis AlbertoSánchez González, BlancaVillamor, NeusBeà, SílviaCampo, EliasSalar, AntonioGiné, EvaLópez Guillermo, ArmandoBellosillo Paricio, BeatrizCell-free DNACopy number analysisMutational profilePrimary mediastinal large B-cell lymphomaHigh-throughput sequencing of cell-free DNA (cfDNA) has emerged as a promising noninvasive approach in lymphomas, being particularly useful when a biopsy specimen is not available for molecular analysis, as it frequently occurs in primary mediastinal large B-cell lymphoma (PMBL). We used cfDNA for genomic characterization in 20 PMBL patients by means of a custom NGS panel for gene mutations and low-pass whole-genome sequencing (WGS) for copy number analysis (CNA) in a real-life setting. Appropriate cfDNA to perform the analyses was obtained in 18/20 cases. The sensitivity of cfDNA to detect the mutations present in paired FFPE samples was 69% (95% CI: 60-78%). The mutational landscape found in cfDNA samples was highly consistent with that of the tissue, with the most frequently mutated genes being B2M (61%), SOCS1 (61%), GNA13 (44%), STAT6 (44%), NFKBIA (39%), ITPKB (33%), and NFKBIE (33%). Overall, we observed a 75% concordance to detect CNA gains/losses between DNA microarray and low-pass WGS. The sensitivity of low-pass WGS was remarkably higher for clonal CNA (18/20, 90%) compared to subclonal alterations identified by DNA microarray. No significant associations between cfDNA amount and tumor burden or outcome were found. cfDNA is an excellent alternative source for the accurate genetic characterization of PMBL cases.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects PI16/00420 and PI19/00887 to A.L.-G. and E.G., PI17/00313 to L.C., PI19/0005 to B.B., and PI19/00034 to A.S., and co-funded by the European Union; CIBERONC [grant numbers CB16/12/00334, CB16/12/00225, and CB16/12/00241]; and the European Union’s Horizon 2020 research and innovation programme and the Canadian Institutes of Health Research [grant number 825835 to E.C.]. F.N. acknowledges the research support from the American Association for Cancer Research (2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research, Grant Number 21-40-11-NADE), the European Hematology Association (EHA Junior Research Grant 2021, Grant Number RG-202012-00245), and the Lady Tata Memorial Trust (International Award for Research in Leukaemia 2021–2022, Grant Number LADY_TATA_21_3223). C.L. is supported by postdoctoral Beatriu de Pinós from Secretaria d’Universitats I Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and by Marie Sklodowska-Curie COFUND program from H2020 (2018-BP-00055). E.C. is an Academia Researcher of the “Institució Catalana de Recerca i Estudis Avançats” (ICREA) [no grant number applies] of the Generalitat de Catalunya. We also acknowledge the support of the CERCA Program from Generalitat de Catalunya [no grant number applies].MDPI202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55508http://dx.doi.org/10.3390/diagnostics12071575reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/EC/H2020/825835Copyright © 2022 by Rivas-Delgado A, Nadeu F, Andrade-Campos M, López C, Enjuanes A, Mozas P, et al. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/555082026-05-29T05:05:01Z
dc.title.none.fl_str_mv Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
title Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
spellingShingle Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
Rivas-Delgado, Alfredo
Cell-free DNA
Copy number analysis
Mutational profile
Primary mediastinal large B-cell lymphoma
title_short Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
title_full Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
title_fullStr Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
title_full_unstemmed Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
title_sort Cell-free DNA for genomic analysis in primary mediastinal large B-cell lymphoma
dc.creator.none.fl_str_mv Rivas-Delgado, Alfredo
Nadeu, Ferran
Andrade-Campos, Marcio
López, Cristina
Enjuanes¸ Anna
Mozas, Pablo
Frigola, Gerard
Colomo Saperas, Luis Alberto
Sánchez González, Blanca
Villamor, Neus
Beà, Sílvia
Campo, Elias
Salar, Antonio
Giné, Eva
López Guillermo, Armando
Bellosillo Paricio, Beatriz
author Rivas-Delgado, Alfredo
author_facet Rivas-Delgado, Alfredo
Nadeu, Ferran
Andrade-Campos, Marcio
López, Cristina
Enjuanes¸ Anna
Mozas, Pablo
Frigola, Gerard
Colomo Saperas, Luis Alberto
Sánchez González, Blanca
Villamor, Neus
Beà, Sílvia
Campo, Elias
Salar, Antonio
Giné, Eva
López Guillermo, Armando
Bellosillo Paricio, Beatriz
author_role author
author2 Nadeu, Ferran
Andrade-Campos, Marcio
López, Cristina
Enjuanes¸ Anna
Mozas, Pablo
Frigola, Gerard
Colomo Saperas, Luis Alberto
Sánchez González, Blanca
Villamor, Neus
Beà, Sílvia
Campo, Elias
Salar, Antonio
Giné, Eva
López Guillermo, Armando
Bellosillo Paricio, Beatriz
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cell-free DNA
Copy number analysis
Mutational profile
Primary mediastinal large B-cell lymphoma
topic Cell-free DNA
Copy number analysis
Mutational profile
Primary mediastinal large B-cell lymphoma
description High-throughput sequencing of cell-free DNA (cfDNA) has emerged as a promising noninvasive approach in lymphomas, being particularly useful when a biopsy specimen is not available for molecular analysis, as it frequently occurs in primary mediastinal large B-cell lymphoma (PMBL). We used cfDNA for genomic characterization in 20 PMBL patients by means of a custom NGS panel for gene mutations and low-pass whole-genome sequencing (WGS) for copy number analysis (CNA) in a real-life setting. Appropriate cfDNA to perform the analyses was obtained in 18/20 cases. The sensitivity of cfDNA to detect the mutations present in paired FFPE samples was 69% (95% CI: 60-78%). The mutational landscape found in cfDNA samples was highly consistent with that of the tissue, with the most frequently mutated genes being B2M (61%), SOCS1 (61%), GNA13 (44%), STAT6 (44%), NFKBIA (39%), ITPKB (33%), and NFKBIE (33%). Overall, we observed a 75% concordance to detect CNA gains/losses between DNA microarray and low-pass WGS. The sensitivity of low-pass WGS was remarkably higher for clonal CNA (18/20, 90%) compared to subclonal alterations identified by DNA microarray. No significant associations between cfDNA amount and tumor burden or outcome were found. cfDNA is an excellent alternative source for the accurate genetic characterization of PMBL cases.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/55508
http://dx.doi.org/10.3390/diagnostics12071575
url http://hdl.handle.net/10230/55508
http://dx.doi.org/10.3390/diagnostics12071575
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/H2020/825835
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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