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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/5/1332 |
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| author | Martina Manzoni Valentina Marchica Paola Storti Bachisio Ziccheddu Gabriella Sammarelli Giannalisa Todaro Francesca Pelizzoni Simone Salerio Laura Notarfranchi Alessandra Pompa Luca Baldini Niccolò Bolli Antonino Neri Nicola Giuliani Marta Lionetti |
| author_facet | Martina Manzoni Valentina Marchica Paola Storti Bachisio Ziccheddu Gabriella Sammarelli Giannalisa Todaro Francesca Pelizzoni Simone Salerio Laura Notarfranchi Alessandra Pompa Luca Baldini Niccolò Bolli Antonino Neri Nicola Giuliani Marta Lionetti |
| author_sort | Martina Manzoni |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:38:50Z |
| format | Article |
| id | doaj.art-9ddd1dfe44b449aa931a918d1f13b6a4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:38:50Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9ddd1dfe44b449aa931a918d1f13b6a42023-11-20T01:29:07ZengMDPI AGCancers2072-66942020-05-01125133210.3390/cancers12051332Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering MyelomaMartina Manzoni0Valentina Marchica1Paola Storti2Bachisio Ziccheddu3Gabriella Sammarelli4Giannalisa Todaro5Francesca Pelizzoni6Simone Salerio7Laura Notarfranchi8Alessandra Pompa9Luca Baldini10Niccolò Bolli11Antonino Neri12Nicola Giuliani13Marta Lionetti14Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Clinical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, 43126 Parma, ItalyHematology, “Azienda Ospedaliero-Universitaria di Parma”, 43126 Parma, ItalyHematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyHematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyHematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, ItalyDepartment of Oncology and Hemato-oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-oncology, University of Milan, 20122 Milan, ItalyDepartment of Oncology and Hemato-oncology, University of Milan, 20122 Milan, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Oncology and Hemato-oncology, University of Milan, 20122 Milan, ItalyGenomic 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.https://www.mdpi.com/2072-6694/12/5/1332multiple myelomapremalignant stagesnext-generation sequencing |
| spellingShingle | Martina Manzoni Valentina Marchica Paola Storti Bachisio Ziccheddu Gabriella Sammarelli Giannalisa Todaro Francesca Pelizzoni Simone Salerio Laura Notarfranchi Alessandra Pompa Luca Baldini Niccolò Bolli Antonino Neri Nicola Giuliani Marta Lionetti Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma Cancers multiple myeloma premalignant stages next-generation sequencing |
| 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 | multiple myeloma premalignant stages next-generation sequencing |
| url | https://www.mdpi.com/2072-6694/12/5/1332 |
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