دورية أكاديمية
The modular network structure of the mutational landscape of Acute Myeloid Leukemia.
| العنوان: | The modular network structure of the mutational landscape of Acute Myeloid Leukemia. |
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| المؤلفون: | Ibáñez, Mariam, Carbonell-Caballero, José, Such, Esperanza, García-Alonso, Luz, Liquori, Alessandro, López-Pavía, María, Llop, Marta, Alonso, Carmen, Barragán, Eva, Gómez-Seguí, Inés, Neef, Alexander, Hervás, David, Montesinos, Pau, Sanz, Guillermo, Sanz, Miguel Angel, Dopazo, Joaquín, Cervera, José |
| سنة النشر: | 2018 |
| المجموعة: | Sistema Sanitario Público de Andalucía (SSPA): Repositorio |
| مصطلحات موضوعية: | Adult, Aged, Cytodiagnosis, Female, Gene Regulatory Networks, Genetic Association Studies, Genetic Heterogeneity, Humans, Karyotype, Leukemia, Myeloid, Acute, Male, Middle Aged, Mutation, Neoplasm Proteins, Nucleophosmin, Prognosis, Exome Sequencing |
| الوصف: | Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | http://hdl.handle.net/10668/13054Test; PMC6179200; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202926&type=printableTest; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179200/pdfTest |
| DOI: | 10.1371/journal.pone.0202926 |
| DOI: | 10.1371/journal.pone.0202926&type=printable |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0202926Test http://hdl.handle.net/10668/13054Test https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202926&type=printableTest https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179200/pdfTest |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; open access |
| رقم الانضمام: | edsbas.A4C04180 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0202926 |