Next Article in Journal
A Bird’s-Eye View of Cell Sources for Cell-Based Therapies in Blood Cancers
Previous Article in Journal
TOM40 Inhibits Ovarian Cancer Cell Growth by Modulating Mitochondrial Function Including Intracellular ATP and ROS Levels
Previous Article in Special Issue
Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
Open AccessArticle

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

Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy
Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy
Department of Clinical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Hematology, “Azienda Ospedaliero-Universitaria di Parma”, 43126 Parma, Italy
Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
Author to whom correspondence should be addressed.
These authors are co-last authors.
Cancers 2020, 12(5), 1332;
Received: 16 March 2020 / Revised: 12 May 2020 / Accepted: 20 May 2020 / Published: 23 May 2020
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and 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 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. View Full-Text
Keywords: multiple myeloma; premalignant stages; next-generation sequencing multiple myeloma; premalignant stages; next-generation sequencing
Show Figures

Figure 1

MDPI and ACS Style

Manzoni, M.; Marchica, V.; Storti, P.; Ziccheddu, B.; Sammarelli, G.; Todaro, G.; Pelizzoni, F.; Salerio, S.; Notarfranchi, L.; Pompa, A.; Baldini, L.; Bolli, N.; Neri, A.; Giuliani, N.; Lionetti, M. Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma. Cancers 2020, 12, 1332.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop