Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Manzoni M

PROVIDER: S-EPMC7281620 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Manzoni Martina M Marchica Valentina V Storti Paola P Ziccheddu Bachisio B Sammarelli Gabriella G Todaro Giannalisa G Pelizzoni Francesca F Salerio Simone S Notarfranchi Laura L Pompa Alessandra A Baldini Luca L Bolli Niccolò N Neri Antonino A Giuliani Nicola N Lionetti Marta M

Cancers 20200523 5

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 ...[more]

PMID: 32456143

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Project description:ObjectivesMetagenomic next-generation sequencing (mNGS) technology is helpful for the early diagnosis of infective endocarditis, especially culture-negative infective endocarditis, which may guide clinical treatment. The purpose of this study was to compare the presence of culture-negative infective endocarditis pathogens versus culture-positive ones, and whether mNGS test results could influence treatment regimens for patients with routine culture-negative infective endocarditis.MethodsThe present study enrolled patients diagnosed with infective endocarditis and tested for mNGS in the First Affiliated Hospital of Zhengzhou University from February 2019 to February 2022 continuously. According to the culture results, patients were divided into culture-negative group (Group CN, n=18) and culture-positive group (Group CP, n=32). The baseline characteristics, clinical data, pathogens, 30 day mortality and treatment regimen of 50 patients with infective endocarditis were recorded and analyzed.ResultsExcept for higher levels of PCT in the Group CN [0.33 (0.16-2.74) ng/ml vs. 0.23 (0.12-0.49) ng/ml, P=0.042], there were no significant differences in the basic clinical data and laboratory examinations between the two groups (all P>0.05). The aortic valve and mitral valve were the most involved valves in patients with infective endocarditis (aortic valve involved: Group CN 10, Group CP 16; mitral valve involved: Group CN 8, Group CP 21; P>0.05) while 9 patients had multiple valves involved (Group CN 2, Group CP 7; P>0.05). The detection rate of non-streptococci infections in the Group CN was significantly higher than that in the Group CP (9/18 vs. 3/32, P=0.004). There was no significant difference in patients with heart failure hospitalization and all-cause death at 30 days after discharge (3 in Group CN vs. 4 in Group CP, P>0.05). It is worth noting that 10 patients with culture-negative infective endocarditis had their antibiotic regimen optimized after the blood mNGS.ConclusionsCulture-negative infective endocarditis should be tested for mNGS for early diagnosis and to guide clinical antibiotic regimen.

Project description:BackgroundMetagenomic next-generation sequencing (mNGS) technology has been widely used to diagnose various infections. Based on the most common pathogen profiles, targeted mNGS (tNGS) using multiplex PCR has been developed to detect pathogens with predesigned primers in the panel, significantly improving sensitivity and reducing economic burden on patients. However, there are few studies on summarizing pathogen profiles of pulmonary infections in immunocompetent and immunocompromised patients in Jilin Province of China on large scale.MethodsFrom January 2021 to December 2023, bronchoalveolar lavage fluid (BALF) or sputum samples from 546 immunocompetent and immunocompromised patients with suspected community-acquired pneumonia were collected. Pathogen profiles in those patients on whom mNGS was performed were summarized. Additionally, we also evaluated the performance of tNGS in diagnosing pulmonary infections.ResultsCombined with results of mNGS and culture, we found that the most common bacterial pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in both immunocompromised and immunocompetent patients with high detection rates of Staphylococcus aureus and Enterococcus faecium, respectively. For fungal pathogens, Pneumocystis jirovecii was commonly detected in patients, while fungal infections in immunocompetent patients were mainly caused by Candida albicans. Most of viral infections in patients were caused by Human betaherpesvirus 5 and Human gammaherpesvirus 4. It is worth noting that, compared with immunocompetent patients (34.9%, 76/218), more mixed infections were found in immunocompromised patients (37.8%, 14/37). Additionally, taking final comprehensive clinical diagnoses as reference standard, total coincidence rate of BALF tNGS (81.4%, 48/59) was much higher than that of BALF mNGS (40.0%, 112/280).ConclusionsOur findings supplemented and classified the pathogen profiles of pulmonary infections in immunocompetent and immunocompromised patients in Jilin Province of China. Most importantly, our findings can accelerate the development and design of tNGS specifically used for regional pulmonary infections.

Dataset Information

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

Publications

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

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