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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Detalles Bibliográficos
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
Descripción
Sumario: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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