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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 principales: Rivas-Delgado, Alfredo, Nadeu, Ferran, Andrade-Campos, Marcio, López, Cristina, Enjuanes, Anna, Mozas, Pablo, Frigola, Gerard, Colomo, Luis, Sanchez-Gonzalez, Blanca, Villamor, Neus, Beà, Sílvia, Campo, Elías, Salar, Antonio, Giné, Eva, López-Guillermo, Armando, Bellosillo, Beatriz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324191/
https://www.ncbi.nlm.nih.gov/pubmed/35885481
http://dx.doi.org/10.3390/diagnostics12071575
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author Rivas-Delgado, Alfredo
Nadeu, Ferran
Andrade-Campos, Marcio
López, Cristina
Enjuanes, Anna
Mozas, Pablo
Frigola, Gerard
Colomo, Luis
Sanchez-Gonzalez, Blanca
Villamor, Neus
Beà, Sílvia
Campo, Elías
Salar, Antonio
Giné, Eva
López-Guillermo, Armando
Bellosillo, Beatriz
author_facet Rivas-Delgado, Alfredo
Nadeu, Ferran
Andrade-Campos, Marcio
López, Cristina
Enjuanes, Anna
Mozas, Pablo
Frigola, Gerard
Colomo, Luis
Sanchez-Gonzalez, Blanca
Villamor, Neus
Beà, Sílvia
Campo, Elías
Salar, Antonio
Giné, Eva
López-Guillermo, Armando
Bellosillo, Beatriz
author_sort Rivas-Delgado, Alfredo
collection PubMed
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.
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spelling pubmed-93241912022-07-27 Cell-Free DNA for Genomic Analysis in Primary Mediastinal Large B-Cell Lymphoma Rivas-Delgado, Alfredo Nadeu, Ferran Andrade-Campos, Marcio López, Cristina Enjuanes, Anna Mozas, Pablo Frigola, Gerard Colomo, Luis Sanchez-Gonzalez, Blanca Villamor, Neus Beà, Sílvia Campo, Elías Salar, Antonio Giné, Eva López-Guillermo, Armando Bellosillo, Beatriz Diagnostics (Basel) Article 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. MDPI 2022-06-28 /pmc/articles/PMC9324191/ /pubmed/35885481 http://dx.doi.org/10.3390/diagnostics12071575 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rivas-Delgado, Alfredo
Nadeu, Ferran
Andrade-Campos, Marcio
López, Cristina
Enjuanes, Anna
Mozas, Pablo
Frigola, Gerard
Colomo, Luis
Sanchez-Gonzalez, Blanca
Villamor, Neus
Beà, Sílvia
Campo, Elías
Salar, Antonio
Giné, Eva
López-Guillermo, Armando
Bellosillo, Beatriz
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324191/
https://www.ncbi.nlm.nih.gov/pubmed/35885481
http://dx.doi.org/10.3390/diagnostics12071575
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