A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms

Liquori, Alessandro; Lesende, Iván; Palomo, Laura; Avetisyan, Gayane; Ibáñez, Mariam; González-Romero, Elisa; Boluda-Navarro, Mireia; Morote-Faubel, Mireya; Garcia‐Ruiz, Cristian; Martínez-Valiente, Cristina; Santiago-Balsera, Marta; Gómez-Seguí, Inés; Sanjuán-Pla, Alejandra; Sanz, Miguel Á.; Sanz, Guillermo; Solé, Françesc; Such, Esperanza; Cervera, José

doi:10.3390/cancers13081947

Cited by 7 publications

(8 citation statements)

References 48 publications

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“…This is the first study to assess the detection of cytogenetic alterations in cfDNA by NGS in a cohort of patients with MDS. Other studies have used NGS to detect these chromosomal alterations in PB or BM samples, 28 and only 1 study used cfDNA to identify the loss of chromosome 9 in cfDNA in a patient with MDS. 11 …”

Section: Discussionmentioning

confidence: 99%

Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA

et al. 2022

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Molecular and cytogenetic studies are essential in patients with myelodysplastic syndromes (MDS) for diagnosis and prognosis. Cell-free DNA (cfDNA) analysis has been reported as a reliable non-invasive approach for detecting molecular abnormalities in MDS, however, there is limited information about cytogenetic alterations and monitoring in cfDNA. We have assessed the molecular and cytogenetic profile of a cohort of 70 patients with MDS by next-generation sequencing (NGS) using cfDNA and compared the results to paired bone marrow (BM) DNA. Sequencing of BM DNA and cfDNA showed a comparable mutational profile (92.1% concordance) and variant allele frequencies (VAF) strongly correlated between both sample types. Of note, SF3B1 mutations were detected with significantly higher VAF in cfDNA than in BM DNA. NGS and microarrays were highly concordant to detect chromosomal alterations although with lower sensitivity than karyotype/FISH. Nevertheless, all cytogenetic aberrations detected by NGS in BM DNA were also detected in cfDNA. Additionally, molecular and cytogenetic alterations were monitored and we observed an excellent correlation between the VAF of mutations in BM DNA and cfDNA across multiple matched time points. A decrease in the cfDNA VAF was detected in patients responding to therapy, but not in non-responding patients. Of note, cfDNA analysis also showed cytogenetic evolution in 2 cases not responding to treatment. In conclusion, although further studies with larger cohorts are required, our results support the analysis of cfDNA as a promising strategy for performing molecular characterization, detection of chromosomal aberrations and monitoring of MDS patients.

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Section: Discussionmentioning

confidence: 99%

Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA

et al. 2022

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“…According to the data reported by Papaemmanuil et al, cytogenetic anomalies were found in about 40–50% of MDS patients [ 16 ]; the most common chromosomal abnormalities are the loss of chromosome 7, deletions of the long arm of chromosomes 5 and 7, and gains of some chromosomes, such as chromosomes 8, 19, and 21 [ 18 , 19 , 20 ].…”

Section: Cytogenetic Of Mds Progressionmentioning

confidence: 99%

The Genetic Landscape of Myelodysplastic Neoplasm Progression to Acute Myeloid Leukemia

Bănescu

Tripon

Muntean

2023

IJMS

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Myelodysplastic neoplasm (MDS) represents a heterogeneous group of myeloid disorders that originate from the hematopoietic stem and progenitor cells that lead to the development of clonal hematopoiesis. MDS was characterized by an increased risk of transformation into acute myeloid leukemia (AML). In recent years, with the aid of next-generation sequencing (NGS), an increasing number of molecular aberrations were discovered, such as recurrent mutations in FLT3, NPM1, DNMT3A, TP53, NRAS, and RUNX1 genes. During MDS progression to leukemia, the order of gene mutation acquisition is not random and is important when considering the prognostic impact. Moreover, the co-occurrence of certain gene mutations is not random; some of the combinations of gene mutations seem to have a high frequency (ASXL1 and U2AF1), while the co-occurrence of mutations in splicing factor genes is rarely observed. Recent progress in the understanding of molecular events has led to MDS transformation into AML and unraveling the genetic signature has paved the way for developing novel targeted and personalized treatments. This article reviews the genetic abnormalities that increase the risk of MDS transformation to AML, and the impact of genetic changes on evolution. Selected therapies for MDS and MDS progression to AML are also discussed.

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“…Identifying genetic mutations and determining how these gene mutations work together to produce MDS phenotypes can help researchers in the eld better understand the pathogenesis of MDS and how MDS translates into acute leukemia. Over the decades, advances in technology have made it possible to identify new genetic mutations in MDS, including SNP array analysis and next-generation sequencing (NGS) identi ng genes that are repeatedly mutated in MDS [13], and the application of whole genome sequencing and exome sequencing can identify more prognostically relevant genetic mutations [14], which not only facilitates targeted drug research against genetic mutations, but also promotes con dence in using genomic, transcriptome, and clinical data to group MDS more granularly for prognostic grouping [15]. In short, gene mutation is a necessary condition for the change of disease phenotype, which provides great possibilities for revealing the internal law of MDS disease.…”

Section: Cluster2 and Cluster6mentioning

confidence: 99%

Bibliometric analysis of the Global Myelodysplastic Syndrome Study 1998-2022

Zhang

et al. 2023

Preprint

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Myelodysplastic syndromes (MDS) is a common myeloid malignancy with a high risk of transformation into acute leukaemia. In recent decades, the treatment of MDS has made great progress, and thousands of papers on MDS treatment-related research have been published. We conducted a bibliometric analysis of the literature on MDS and discussed collaboration between authors, countries and institutions, identifying research hotspots in the field of MDS. We searched the Web of Science (core collection) on the subject of "Myelodysplastic syndromes" or "Myelodysplastic syndromes" from January 1998 to September 2022, and analyzed the year of publication, research direction, country, institution, journal, distribution of authors, In addition, visual analysis was performed with CiteSpace, VOSviewer, Gephi, Charticulator, Scimago Graphica, and network graphs were generated to evaluate collaborations between different authors, countries, and institutions and the year of outbreak in keyword concentration, as well as the time zone map display of keywords. We searched 5218 articles from WOSCC as of September 29, 2022, and we found that the number of publications fluctuated from 1998 to 2008, remained relatively stable, and showed a slow upward trend in the following years. The most published countries are the United States, Germany and Italy, and the most cited country is Sweden, where the close collaborative research of the National House is crucial to progress in the field of MDS. Since 1998, hematopoietic stem cell transplantation and post-transplantation prognosis risk research has been a research hotspot, until 2009, the discovery of azacitidine and other demethylation drugs provided new treatment strategies in the field of MDS, more and more clinical trials are committed to finding new targeted drugs and exploring new prognostic risk factors for MDS, MDS treatment and prognosis have also received continuous attention. Bibliometric analysis of MDS-related research can help researchers and clinicians quickly understand the research hotspots and development trends in this field, provide researchers with new research angles, and provide ideas for the development of new treatment strategies.

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A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms

Cited by 7 publications

References 48 publications

Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA

Molecular and cytogenetic characterization of myelodysplastic syndromes in cell-free DNA

The Genetic Landscape of Myelodysplastic Neoplasm Progression to Acute Myeloid Leukemia

Bibliometric analysis of the Global Myelodysplastic Syndrome Study 1998-2022

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