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
| العنوان: | 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 |
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| المؤلفون: | Liquori, Alessandro, Lesende, Iván, Palomo Sanchís, Laura, Avetisyan, Gayane, Ibáñez, Mariam, González-Romero, Elisa, Boluda-Navarro, Mireia, Morote-Faubel, Mireya, Garcia-Ruiz, Cristian, Martinez-Valiente, Cristina, Santiago-Balsera, Marta, Gomez-Seguí, Inés, Sanjuan-Pla, Alejandra, Sanz, Miguel A., Sanz, Guillermo, Sole, F., Such, Esperanza, Cervera, José, Universitat Autònoma de Barcelona |
| المصدر: | Cancers r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe Volume 13 Issue 8 Cancers, Vol 13, Iss 1947, p 1947 (2021) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Myeloid, myeloid neoplasm, Concordance, Gene mutation, Article, cytogenetics, Loss of heterozygosity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, SNP, RC254-282, business.industry, Myelodysplastic syndromes, Cytogenetics, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, myelodysplastic syndromes, karyotype, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, next-generation sequencing, business, SNP array |
| الوصف: | Simple Summary Chromosomal abnormalities and somatic mutations are found in patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in around 50-80% of cases. The identification of these alterations is important for the accurate diagnosis and prognostic classification of these patients. Often, an apparently normal or failed karyotype might lead to an inadequate estimation of the prognostic risk, and several strategies should be combined to solve these cases. The aim of this study was to introduce a novel next-generation sequencing (NGS)-based strategy for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this approach on a large cohort of patients by comparing our findings with those obtained with standard-of-care methods (i.e., karyotype and SNP-arrays). We show that our platform represents a significant improvement on current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders. Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk. Here, we present a novel targeted NGS-based assay for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this platform in a large cohort of patients by performing a one-to-one comparison with the lesions from karyotype and single-nucleotide polymorphism (SNP) arrays. Our strategy demonstrated an approximately 97% concordance with standard clinical assays, showing sensitivity at least equivalent to that of SNP arrays and higher than that of conventional cytogenetics. In addition, this NGS assay was able to identify both copy-neutral loss of heterozygosity events distributed genome-wide and copy number alterations, as well as somatic mutations within significant driver genes. In summary, we show a novel NGS platform that represents a significant improvement to current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de690083e52161487f1f87c5ecca3bceTest http://europepmc.org/articles/PMC8072643Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....de690083e52161487f1f87c5ecca3bce |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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