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Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma

Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic set...

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Autores principales: Manzoni, Martina, Marchica, Valentina, Storti, Paola, Ziccheddu, Bachisio, Sammarelli, Gabriella, Todaro, Giannalisa, Pelizzoni, Francesca, Salerio, Simone, Notarfranchi, Laura, Pompa, Alessandra, Baldini, Luca, Bolli, Niccolò, Neri, Antonino, Giuliani, Nicola, Lionetti, Marta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281620/
https://www.ncbi.nlm.nih.gov/pubmed/32456143
http://dx.doi.org/10.3390/cancers12051332
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author Manzoni, Martina
Marchica, Valentina
Storti, Paola
Ziccheddu, Bachisio
Sammarelli, Gabriella
Todaro, Giannalisa
Pelizzoni, Francesca
Salerio, Simone
Notarfranchi, Laura
Pompa, Alessandra
Baldini, Luca
Bolli, Niccolò
Neri, Antonino
Giuliani, Nicola
Lionetti, Marta
author_facet Manzoni, Martina
Marchica, Valentina
Storti, Paola
Ziccheddu, Bachisio
Sammarelli, Gabriella
Todaro, Giannalisa
Pelizzoni, Francesca
Salerio, Simone
Notarfranchi, Laura
Pompa, Alessandra
Baldini, Luca
Bolli, Niccolò
Neri, Antonino
Giuliani, Nicola
Lionetti, Marta
author_sort Manzoni, Martina
collection PubMed
description Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we performed a targeted gene mutation analysis and a genome-wide assessment of copy number alterations (CNAs) by ultra-low-pass whole genome sequencing (ULP-WGS) in six patients with monoclonal gammopathy of undetermined significance and 25 patients with smoldering MM (SMM). Our comprehensive genomic characterization highlighted heterogeneous but substantial values of the tumor fraction, especially in SMM; a rather high degree of genomic complexity, in terms of both mutations and CNAs, and inter-patient variability; a higher incidence of gene mutations and CNAs in SMM, confirming ongoing evolution; intraclonal heterogeneity; and instances of convergent evolution. ULP-WGS of these patients proved effective in revealing the marked genome-wide level of their CNAs, most of which are not routinely investigated. Finally, the analysis of our small SMM cohort suggested that chr(8p) deletions, the DNA tumor fraction, and the number of alterations may have clinical relevance in the progression to overt MM. Although validation in larger series is mandatory, these findings highlight the promising impact of genomic approaches in the clinical management of SMM.
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spelling pubmed-72816202020-06-17 Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma Manzoni, Martina Marchica, Valentina Storti, Paola Ziccheddu, Bachisio Sammarelli, Gabriella Todaro, Giannalisa Pelizzoni, Francesca Salerio, Simone Notarfranchi, Laura Pompa, Alessandra Baldini, Luca Bolli, Niccolò Neri, Antonino Giuliani, Nicola Lionetti, Marta Cancers (Basel) Article Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we performed a targeted gene mutation analysis and a genome-wide assessment of copy number alterations (CNAs) by ultra-low-pass whole genome sequencing (ULP-WGS) in six patients with monoclonal gammopathy of undetermined significance and 25 patients with smoldering MM (SMM). Our comprehensive genomic characterization highlighted heterogeneous but substantial values of the tumor fraction, especially in SMM; a rather high degree of genomic complexity, in terms of both mutations and CNAs, and inter-patient variability; a higher incidence of gene mutations and CNAs in SMM, confirming ongoing evolution; intraclonal heterogeneity; and instances of convergent evolution. ULP-WGS of these patients proved effective in revealing the marked genome-wide level of their CNAs, most of which are not routinely investigated. Finally, the analysis of our small SMM cohort suggested that chr(8p) deletions, the DNA tumor fraction, and the number of alterations may have clinical relevance in the progression to overt MM. Although validation in larger series is mandatory, these findings highlight the promising impact of genomic approaches in the clinical management of SMM. MDPI 2020-05-23 /pmc/articles/PMC7281620/ /pubmed/32456143 http://dx.doi.org/10.3390/cancers12051332 Text en © 2020 by the authors. 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/).
spellingShingle Article
Manzoni, Martina
Marchica, Valentina
Storti, Paola
Ziccheddu, Bachisio
Sammarelli, Gabriella
Todaro, Giannalisa
Pelizzoni, Francesca
Salerio, Simone
Notarfranchi, Laura
Pompa, Alessandra
Baldini, Luca
Bolli, Niccolò
Neri, Antonino
Giuliani, Nicola
Lionetti, Marta
Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
title Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
title_full Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
title_fullStr Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
title_full_unstemmed Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
title_short Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
title_sort application of next-generation sequencing for the genomic characterization of patients with smoldering myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281620/
https://www.ncbi.nlm.nih.gov/pubmed/32456143
http://dx.doi.org/10.3390/cancers12051332
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